ISCHEMIC STROKE

DEFINITION
 Stroke is defined as a syndrome of rapid onset of cerebral deficit (usually
focal) lasting >one h or leading to death, with no cause apparent other than
a vascular one.
 An interruption of blood supply to a vital center in the brain.
 Also called “brain attack”, cerebral infarction, cerebral hemorrhage,
ischemic stroke or stroke.

Stroke – Risk Factors

 Modifiable
– Hypertension
– Tobacco use

– Hx of TIA’s
– Heart Disease
– Diabetes Mellitus
– Hypercoagulopathy
 Pregnancy, cancer, etc.
– Sickle Cell and increased RBC
– Hx of carotid Bruit

 Unmodifiable
– Age
– Gender
– Race
– Previous CVA
– Heredity

CAUSES OF ISCHEMIC STROKE

 •Arrhythmias
  •Valve disease
 •Dilated cardiomyopathy
 •Recent myocardial infarction
 •Paradoxical emboli

 •Aorta Large-vessel disorders

 •Atherosclerosis or dissection in the carotid or vertebrobasilar system
Small-vessel occlusive disease
 •Hypertension-induced disease

 •Isolated central nervous system angiitis

 •Systemic lupus erythematosus Hematologic disorders
 •Polycythemia
 •Thrombocytosis
 •Severe leukocytosis (acute leukemia)
 •Antithrombin III deficiency

 •Protein C deficiency,
 •Protein S deficiency
 •Factor V Leiden mutation
 •Hypercoagulable state
Pathology
 Ischemia of brain occurs due to thromboembolic event .

 Reduction of blood flow reduces supply of oxygen and hence ATP.

 H+ is produced by anaerobic metabolism of available glucose.
 Energy-dependent membrane ionic pumps fail, leading to cytotoxic
oedema and membrane depolarisation, allowing calcium entry and
releasing glutamate
 Calcium enters cells via glutamate-gated channels and activates
destructive intracellular enzymes, destroying intracellular organelles and
cell membrane, with release of free radicals.
  Free fatty acid release activates pro-coagulant pathways that exacerbate
local ischemia.

 Glial cells take up H+, can no longer take up extracellular glutamate and
also suffer cell death, leading to liquefactive necrosis of whole arterial
territory.

Signs of Stroke
 Sudden numbness or weakness in the face, arm, or leg, especially on one
side of the body.
 Sudden confusion, trouble speaking, or difficulty understanding speech.
 Sudden trouble seeing in one or both eyes.
 Sudden trouble walking, dizziness, loss of balance, or lack of
coordination.
 Sudden severe headache with no known cause.

Stroke – Signs and Symptoms

 Ischemic

– Carotid Circulation
 Unilateral paralysis (opposite side)
 Numbness (opposite side)
 Language disturbance
– Aphasia – difficult comprehension, nonsense,
difficult reading/writing
– Dysarthria – slurred speech, abnormal
pronunciation.

 Visual disturbance (opposite side)

 Monocular blindness (same side)
 Ischemic
– Vertebrobasilar Circulation
 Vertigo
  Visual disturbance
– Both eyes simultaneously
 Diplopia
– Ocular palsy – inability to move to one side

– Dysconjugate gaze – asynchronous movement

 Paralysis
 Numbness
 Dysarthria
 Ataxia

Differential Diagnosis of Stroke

– Head/Cervical trauma
– Meningitis/encephalitis
– Hypertensive encephalopathy
– Intracranial mass
 Tumor

 Sub/epi dural hematoma

– Todd’s paralysis
– Migraine w/ neuro sx
– Metabolic
 Hyper/hypo glycemia
 Post arrest ischemia

Stages of CVA
 Transient ischemic attack (TIA) – sudden and short-lived attack.
 Reversible ischemic neurologic deficit (RIND) similar to TIA, but
symptoms can last up to a week.
  Stroke in evolution (SIE) - gradual worsening of symptoms of brain
ischemia.

 Completed stroke (CS) – symptoms of stroke stable over a period and

rehab can begin.

Stroke - Management
 ER Diagnostic Studies

– CT scan – done w/in 25 mins, read w/in 45 mins

 r/o hemorrhage
 Often normal early in ischemic stroke
– EKG
 Changes may be caused by or cause of stroke
– MRA (Magnetic Resonance Angiography)

– Cerebral Angiography

Management (General Management)

Airway – Perform bedside swallow screen and keep patient nil by mouth if
swallowing unsafe or aspiration occurs

• Breathing – Check respiratory rate and oxygen saturation and give oxygen if
saturation < 95%

• Circulation – Check peripheral perfusion, pulse and blood pressure and treat
abnormalities with fluid replacement, anti-arrhythmics and inotropic drugs
as appropriate

• Hydration – If signs of dehydration, give fluids parenterally or by nasogastric

tube

• Nutrition. Assess nutritional status and provide nutritional supplements if

necessary – If dysphagia persists for > 48 hrs, start feeding via a
nasogastric tube

• Medication – If patient is dysphagic, consider alternative routes for essential

medications
• Blood pressure – Unless there is heart or renal failure, evidence of hypertensive
encephalopathy or aortic dissection, do not lower blood pressure in first
week as it may reduce cerebral perfusion.

• Target blood pressure in patients who are not candidates for rt-PA should
have a systolic blood pressure of less than 220 mm Hg and a diastolic
blood pressure of less than 120 mm Hg.

• A blood pressure less than these values does NOT warrant anti-
hypertensive medicines.

• Blood pressure often returns towards patient’s normal level within first
few days

• Temperature – Increased body temperature in the setting of acute stroke is

associated with poor neurologic outcomes as raised

brain temperature may increase infarct volume

• – If pyrexic, investigate and treat underlying cause & control with

antipyretics

• – Common reasons are aspiration pneumonia, IV line phlebitis and

urinary tract infection.

Pressure areas

• Reduce risk of skin breakdown

• – Treat infection

• – Maintain nutrition

• – Provide pressure-relieving mattress

• – Turn immobile patients regularly

• Incontinence

• Check for constipation and urinary retention; treat appropriately

• Avoid urinary catheterisation unless patient is in acute urinary retention or

incontinence is threatening pressure areas
• Mobilisation

• Avoid bed rest

Thrombolysis

IV thrombolytic therapy with recombinant tissue plasminogen activator (rtPA;

0.9 mg/kg to a maximum of 90 mg, with 10% given as a bolus over 1 minute
and the remainder over 1 hour) is effective in reducing the neurologic deficit in
selected patients.

• Patients should receive tPA within 1 hour after arriving to the hospital but not
more than 4.5 hours after the onset of ischemic symptoms

In patients not eligible for thrombolytic therapy, the immediate

administration of antiplatelets orally daily is indicated.

• Anticoagulant drugs ONLY be started in the setting of atrial fibrillation with

warfarin (target INR 2.0–3.0) or dabigatran (150 mg twice daily)

Elevated intracranial pressure is managed by head elevation and osmotic

agents such as mannitol.

• Decompressive hemicraniectomy for malignant middle cerebral artery

infarctions may reduce mortality and improve functional outcome in some
instances.

Physical Therapy

• Passive movements at an early stage will help prevent contractures. • As

cooperation increases and some recovery begins, active movements will
improve strength and coordination.

• In all cases, early mobilization and active rehabilitation are important. •

Occupational therapy may improve morale and motor skills • Speech therapy
may help expressive dysphasia or dysarthria.

Secondary Prevention

• Antithrombotic therapy
– Aspirin in a dose ranging from 75 to 300 mg is efficacious in stroke
prevention.

– Clopidogrel is marginally better at increased cost and is therefore suggested in

those with concomitant peripheral vascular disease and / or intolerance to
aspirin.

• Dose adjusted warfarin is suggested in an INR 2-3 for those who have
intermittent or continous atrial fibrillation.

Lipid Control

– Atorvastatin 80 mg/day significantly reduced the risk of stroke in patients who

previously had a stroke or (TIA) and who had no known cardiovascular disease.

– Target goal for cholesterol lowering LDL-C of <100 mg/dL and LDL-C of
<70 mg/dL for very-high-risk persons with multiple risk factors

• Blood Pressure Control

– Mean blood pressure fall of 5 mm Hg leads to a one third reduction of stroke

– If BP > 130/70 mmHg 1–2 weeks after onset use thiazide diuretic and/or ACE
inhibitor 1.

Smoking

• Obesity

• Exercise- regular physical activity

• Dietry salt restriction

Surgical Interventions

Carotid Endarterectomy

When arteriography reveals a surgically accessible highgrade stenosis (70–99%

in luminal diameter) on the side appropriate to carotid ischemic attacks

- operative treatment (carotid endarterectomy) or endovascular intervention

reduces the risk of ipsilateral carotid stroke
 Intracranial hemorrhage
Definition
• An intracranial hemorrhage is a type of bleeding that occurs inside the
skull (cranium).

• Bleeding around or within the brain itself is known as a

cerebral hemorrhage (or intracerebral hemorrhage).

Causes
1. High blood pressure is the most common cause of ICH.
2. Head injury or trauma
3. Ruptured cerebral aneurysm (a weak spot in a blood vessel that bursts), or
arteriovenous malformation (a grouping of malformed blood vessels in
your brain that disrupts normal blood flow)

4. Use of blood thinners

5. Bleeding tumors
6. Cocaine or methamphetamine use
7. Bleeding disorders (for example, hemophilia or sickle cell anemia)

Symptoms
• Symptoms usually appear suddenly during ICH.

• They include headache, weakness, confusion, and paralysis, particularly

on one side of your body.

Symptoms of ICH include

• sudden weakness, tingling, or paralysis in your face, arm, or leg,
especially if it occurs on only one side of your body
• sudden onset of severe headache
 • trouble with vision in one or both eyes
• trouble with language skills (reading, writing, speaking, understanding)

• nausea, vomiting

• apathy, sleepiness, lethargy, loss of consciousness, confusion, delirium,

SEIZURES
Types
 Multiple Sclerosis
Multiple sclerosis (MS) is a chronic debilitating CNS immune system disease that
affects the lives of 2.3 million people worldwide, according to National Multiple
Sclerosis Society.

Multiple sclerosis (MS) is considered an autoimmune disease driven mainly by T

cells and mediated by macrophages. Also, other immune system cells (B cells &
regulatory T cells) with injury to oligodendrocytes that form myelin. All
contribute to cause this inflammatory demyelinating disease of the human CNS. It
is the most common disease of the CNS that affects young adults (20-40) years
old. Female to male ratio is 2.5:1 or 3:1. It’s the most common neurological cause
of disability in young adults.

Multiple Sclerosis Etiology

The etiology is not well understood, but most probably is multifactorial (genetic
and environmental). It’s characterized by inflammation, demyelination, axonal
loss and degeneration. There is a debate about the neurodegenerative character of
the disease, whether inflammation initiates neurodegeneration or
neurodegeneration occurs independent of inflammation.

Etiology Risk Factors of MS onset:

Genetics:

Multiple risk genes were identified; complicated genetics with multiple genes
interacting.
 Increased risk in relatives: identical twins 30% risk, child or sibling of person
with MS 3-5%

Demographic:

Female sex

Geography: higher latitudes is associated with higher MS prevalence

Geographical distribution of MS

MS is present in all regions of the world.

Its prevalence varies greatly:

Highest in North America and Europe with highest in Europe in Sweden, and
lowest in Albania.

Lowest in Sub-Saharan Africa and East Asia.

Infections:

EBV:

Almost all MS patients are seropositive for EBV antibodies

Increased MS risk in those who suffer from infectious mononucleosis (glandular

fever).

Smoking:

Smoking increases MS risk and more risk with heavy smokers.

Sunlight:

UV light: higher sun exposure in childhood/ adolescence reduced MS risk.

Vitamin D:

Low vitamin D levels is associated with higher rates of MS.

Obesity:

Obesity increases MS risk.

Viral associations with MS:

EBV

VZV

HHV-6

Measles & Morbilliviruses

Modifiable risk factors for MS onset should be targeted for MS prevention:

smoking

obesity

sunlight exposure

vitamin D deficiency

Structures involved in MS

A white matter disease

White matter plaques:

Classic features

Appears with conventional MRI

Grey matter is also involved:

Cortical & deep grey matter structures

MS is classically characterized by inflammation and destruction of myelin.

Demyelination is an important and well known aspect of MS.

Axonal damage has gained attention recently and there is now substantial
evidence that it has a pivotal role in the disease.

Clinical presentations
Various clinical presentations have been reported depending on the involved area
of the CNS (brain, spinal cord & optic nerves).

Clinical presentations can be:

Focal or multifocal (one or multiple lesions) or disseminated.

Relapses/Attacks (Relapsing MS) OR gradual worsening of neurological

symptoms (Progressive MS).

Symptoms include paraesthesias or numbness or burning sensation or electric like

sensation esp. with spinal cord lesions, weakness in one or more limbs, or visual
disturbances (retrobulbar neuritis or optic neuritis), ocular palsy resulting in
double vision (diplopia), gait disturbances, coordination defects (limb or gait
ataxia), cognitive impairment, depression , heat intolerance (Uhthoff’s
phenomenon), electrical shocks down the spine on neck flexion (Lhermitte’s
phenomenon).

and bladder control problems : urgency, hesitancy, partial retention of urine or

slight incontinence and also constipation are common in spinal cord lesions.
Urinary and fecal incontinence may occur in advanced cases. Erectile dysfunction
and genital hypoesthesia.

Clinical Examination of MS

1) Mental:

Apathy or inattention may occur, emotional lability is common. Euphoria occurs

in some patients; pseudobulbar palsy, a reactive depression in others.

2) Speech:

Scanned speech, staccato speech, slurred speech.

3) Cranial nerves:

Optic neuritis; papilledema, optic atrophy, temporal pallor, retrobulbar neuritis;

normal fundus exam.

Changes in visual field (field defects) by confrontation method

Ophthalmoplegia with diplopia. Nystagmus; either cerebellar or vestibular
nucleus lesion.

4) Motor:

Brisk DTJs, Babinski sign & clonus are often present. Superficial reflexes,
particularly upper and lower abdominal, are diminished or absent.

Muscular weakness and spasticity due to corticospinal lesions produce a stiff,

imbalanced gait, later on the combination of

Spasticity and cerebellar ataxia may become totally disabling.

Cerebral lesions may result in hemipariesis. Sometimes, painful flexor spasms

spontaneously or in response to sensory stimuli.

5) Sensory:

Sensory defects, dysesthesias

Optic Neuritis

Inflammation of the optic nerve

Classic and common presentation

Not always caused by MS, doesn’t always progress to MS

Usually unilateral at a single point of time, rarely bilateral

Blurred vision, visual field defects, diminished V.A, impaired color vision

V.A, fundus exam., and field assessment

VEP (visual evoked potential)

Steroid treatment (pulse steroids)

Uhthoff’s phenomenon

Worsening of neurological symptoms in demyelinating conditions when the body

gets overheated from hot weather, exercise, fever, saunas or spas.
Increased body temperature causes blocking or slowing of nerve impulses in the
damaged nerve.

Once body temperature normalizes, symptoms improve or disappear.

Lhermitte’s phenomenon

Electrical sensation that runs down the

back & into the limbs on neck flexion.

This sign suggests a lesion in the upper

part of the spinal cord (deep sensory).

It’s a Classic MS sign but can occur in

other conditions also.

Investigations in MS

Neuroimaging:

MRI is the most sensitive diagnostic imaging technique, may show plaques.
Gadolinium-contrast enhancement can distinguish areas of active inflammation
from older brain plaques.

CSF:

CSF is abnormal in the majority of patients. IgG are high and lymphocytes and
protein content may be slightly increased. Oligoclonal bands, which indicate IgG
synthesis, can be detected in CSF of patients with MS, but absence of these bands
does not rule out MS. IgG levels correlate with disease severity.

Evoked Potentials:

VEP (Visual Evoked Potential):

P100 is delayed in optic neuritis or at any point in the retinocortical pathway.

Diagnostic Criteria for MS:

2017 Revisions to McDonald Criteria

CNS lesions separated in space and time

The following changes were made for patients with typical clinically isolated
syndrome (CIS):

Positive CSF allows for MS diagnosis where DIS criteria is met

Cortical lesions can be used to demonstrate DIS

Eliminate more likely diagnoses

Specific Drug Therapy in MS

Pulse therapy:

during relapse

IV infusion of Solumedrol (methylprednisolone 1000 mg/day) for 3-5 days,

repeated every time the patient has relapse.

It may shorten the symptomatic period during attacks.

Patients with acute severe optic neuritis may delay the onset of MS by using high
dose IV corticosteroids.

Immunomodulatory,Immunosuppressive and immune reconstitution

Therapies in MS
 Approach to spinal cord disorders
Clinical characteristics

• Sudden: Vascular or Traumatic

• Rapid(Acute): Inflammatory
• Chronic: Degenerative or Tumor

Main clinical manifestations

• Motor: Quadriparesis/Paraparesis
• Sensory: superficial and deep sensory level
• Autonomic(sphincters): urinary and stool incontinence, retention

Classification:
• Complete spinal cord: involvement of all the tracts

• Brown Séquard or hemi-spinal cord syndrome: ipsilateral cortico-spinal

tract, posterior columns and contralateral spinothalamic tract

• Anterior spinal cord syndrome: anterior horns, corticospinal,

spinothalamic and autonomic tracts.
• Posterior spinal cord syndrome: posterior columns
 • Cauda equina: cauda equina nerves

Differential Diagnosis of Compressive spinal cord lesions

• Vascular: AVM
• Traumatic: Disc herniation
• Inflammatory(infection): Pott’s disease (cold abscess) (TB)

• Tumors: Meningioma, Neurofibroma

• Degenerative: syringomyelia 2ry to Arnold chiari malformation

Differential Diagnosis of Non-Compressive spinal cord lesions

• Vascular: Anterior spinal artery occlusion
• Inflammatory(Myelitis):
 Infectious: HSV,HZV,EBV,CMV.

 Post-infectious
 Autoimmune: Multiple sclerosis, Neuromyelitis optica, SLE, Sarcoidosis,
ADEM (acute disseminated encephalomyelitis)
• Metabolic: Vitamin B12 deficiency(Subacute combined degenration)

Disc prolapse
• Commonly lumbosacral, Cervical
• Clinical manifestations:
Extramedullary: Root pain, Motor (LMN, UMN),Late sphincters, Brown-
Sequard syndrome
• Investigations: MRI spine

Spinal Artery occlusion (Cord infarction)

• Commonly due to anterior spinal artery thrombosis(supplying anterior 2/3
of spinal cord)
• Clinical Manifestations:
ASA thrombosis: sudden onset para/quadriparesis, retention, superficial
sensory level(sparing deep sensation)
 Transverse Myelitis
• Viral (Herpes, CMV, EBV) or post-infectious

• Clinical Manifestations:
Intramedullary(complete cord syndrome): Quadri/para-paresis, sensory
level, sphincter disturbance

• Investigations: CSF analysis: High proteins, cells (infection), MRI spine:

Intramedullary inflammatory patch

Potts disease
• known as tuberculous spondylitis, is a classic presentation of
extrapulmonary tuberculosis (TB).
• Commonest site: Dorsal and lumbar spine

• Lead to: Destruction of vertebrae(wedge fracture), sparing intervertebral

disc, cold abscess…………….. Spinal cord compression
• Clinical manifestations:

• Extramedullary: Gradual progressive paraparesis, urinary

incontinence(late), sensory level, vertebral and root pain
• Rarely acute onset (spinal ischemia due to endarteritis obliterans)
• Investigations

• CSF: High lymphocytes, Positive PCR for TB

• MRI: Wedge fracture, Amalgamation, Cold abscess

Multiple sclerosis
• Chronic demyelinating disease affecting CNS and ccc by dissemination in
time and space

• Commonly affect Cervico-dorsal spine(mainly cortico-spinal tract,

posterior column tract)
• Clinical manifestations:

Spinal: paraparesis, incontinence, sensory level(mainly deep sensory)

Extraspinal: impaired Visual acuity(unilateral optic neuritis), cerebellar
ataxia, Diplopia without squint, hemiparesis
 Investigations:

CSF: positive oligoclonal bands

MRI spine: Single or multiple demyelinating patches(not exceeding one

segment)
MRI brain: Multiple demyelinating patches (periventricular, brainstem,
cerebellar,…)

Neuromyelitis optica (Devics disease)

• Autoimmune disease affecting spinal cord, optic nerve
• Commonly affect cervical and dorsal spinal cord

• Clinical manifestations:
Spinal: Complete cord syndrome(as transverse myelitis)
Optic: bilateral optic neuritis
• Investigations:

CSF: positive Aquaporin-4 AB

MRI spine: Intramedullary inflammatory patch (long segment)
MRI brain: usually normal
 Epilepsy

An epileptic seizure is a transient occurrence of signs and/or symptoms due to

abnormal excessive or synchronous neuronal activity in the brain. Epilepsy is a disorder
of the brain characterized by predisposition to generate epileptic seizures. Some
definitions of epilepsy require that seizures be recurrent and unprovoked, but others
require only a single seizure combined with brain alterations which increase the chance
of future seizures.

Epilepsy is a disease of the brain defined by any of the following conditions

A least two unprovoked (or reflex) seizures occurring >24 h apart

One unprovoked (or reflex) seizure and a probability of further seizures similar to the
general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the
next 10 years

Diagnosis of an epilepsy syndrome

Epilepsy is considered to be resolved for individuals who had an age-dependent epilepsy

syndrome but are now past the applicable age or those who have remained seizure-free
for the last 10 years, with no seizure medicines for the last 5 years.

The way that I like to think about it diagnostically and prognostically:

1- Provoked seizures: caused by metabolic derangements, electrolyte

disturbances or drug use/withdrawl.

2- unprovoked seizures: may be A- Idiopathic epilepsy. B- Secondary

epilepsy (Infection, inflammatory state, structural cause as stroke).

Definition of seizures: a group of syndromes characterized by paroxysmal

transient disturbances of brain function that may be manifested as
-Episodic impairment or loss of consciousness,
-Abnormal motor phenomena,
-Psychic or sensory disturbances, or
-Disturbance of the autonomic nervous system; and
These symptoms are due to disturbance of the electrical activity
of the brain.
Epidemiology: About 50 million people worldwide have epilepsy. Epilepsy is
more likely to occur in young children or people over the age of 65 years;
however, it can occur to anyone at any time. Epilepsy is usually controlled, but
not cured, with medication. However, over 30% of people with epilepsy do not
have seizure control even with the best available medications. Surgery may be
considered in difficult cases. Not all epilepsy syndromes are lifelong – some
forms are confined to particular stages of childhood. Epilepsy should not be
understood as a single disorder, but rather as syndromic with divergent
symptoms.
Classifications:
Seizure types:
• GENERALIZED SEIZURES

1-Tonic clonic (in any combination).

2-Absence: A- Typical B- Atypical C-Absence with special features:
(myoclonic absence and absence with eyelid myoclonia).
3-Myoclonic: A- Myoclonic alone B- Myoclonic atonic C-Myoclonic tonic
4- Clonic.
5-Tonic.
6-Atonic.

• FOCAL SEIZURES
Localization-related seizures, sometimes termed partial or focal seizures, arise
from an epileptic focus, (a small portion of the brain that serves as the irritant
driving the epileptic response.). Generalized seizures, in contrast, arise from
many independent foci (multifocal epilepsies) or from epileptic circuits that
involve the whole brain.
Descriptors of focal seizures according to degree of impairment during
seizure: 1- Without impairment of consciousness/responsiveness + with
observable motor or autonomic components (roughly corresponds to the concept
of “simple partial seizure"). 2- With impairment of
consciousness/responsiveness (roughly corresponds to the concept of complex
partial seizure). 3- Evolving to a bilateral, convulsive seizure (involving tonic
and clonic components; replaces the term secondarily generalized seizure).

Epilepsy syndromes: Epilepsy syndromes are further divided by hypothetical

cause: Idiopathic epilepsies are thought to arise from genetic abnormalities that
lead to alteration of basic neuronal regulation. Symptomatic epilepsies arise from
the effects of an epileptic lesion, whether that lesion is focal, such as a tumor, or a
defect in metabolism causing widespread injury to the brain. Epilepsies
attributed to structural-metabolic causes (Tumor, infection, trauma, angioma,
peri-natal insults Stroke, etc.) Just as there are many types of seizures,
there are many types of epilepsy syndromes. Each type of epilepsy syndrome
presents with its own unique combination of: seizure type, typical age of onset,
EEG findings, treatment, and prognosis.

1-Childhood absence epilepsy (CAE):

Is an idiopathic generalized epilepsy that affects children between the ages of 4
and 12 years of age, although peak onset is around five to six years old. These
patients have recurrent absence seizures, brief episodes of unresponsive staring,
sometimes with minor motor features such as eye blinking or subtle chewing. The
EEG finding in CAE is generalized 3 Hz spike and wave discharges. It is more
common in girls than boys. Some go on to develop generalized tonic-clonic
seizures. This condition carries a good prognosis because children do not usually
show cognitive decline or neurological deficits, and the seizures in the majority
cease spontaneously with onging maturation. Seizures are believed to originate
in the thalamus, where there is an abundance of calcium channels. Treatment of
patients with absence seizures only is mainly with sodium valproate or
ethosuximide, which are of equal efficacy controlling absences in around 75% of
patients
2-Juvenile myoclonic epilepsy (JME): is an idiopathic generalized epilepsy that
occurs in patients aged 8 to 20 years. Patients have normal cognition and are
otherwise neurologically intact. The most common seizures are myoclonic jerks,
although generalized tonic-clonic seizures and absence seizures may occur as
well. Myoclonic jerks usually cluster in the early morning after awakening. The
EEG reveals generalized 4–6 Hz spike wave discharges or multiple spike
discharges. Interestingly, these patients are often first diagnosed when they have
their first generalized tonic-clonic seizure later in life, when they experience sleep
deprivation. Alcohol withdrawal can also be a major contributing factor in
breakthrough seizures, as well. The risk of the tendency to have seizures is
lifelong; however, the majority has well controlled seizures with anticonvulsant
medication and avoidance of seizure precipitants.
3-Temporal lobe epilepsy (TLE): A symptomatic localization-related epilepsy,
is the most common epilepsy of adults who experience seizures poorly controlled
with anticonvulsant medications. In most cases, the epileptogenic region is found
in the midline (mesial) temporal structures (e.g., the hippocampus, amygdala, and
parahippocampal gyrus). Seizures begin in late childhood and adolescence. Most
of these patients have complex partial seizures sometimes preceded by an aura,
and some TLE patients also suffer from secondary generalized tonic-clonic
seizures. If the patient does not respond sufficiently to medical treatment,
epilepsy surgery may be considered. Symptoms may include: 1- Ascending
epigastric sensation or visceral aura. 2-Ictal Fear. 3-Oro-alimentary
automatisms. 4-Disturbed conscious level. 5-Partial amnesia. 6-Fugue. 7-
Uncinate fits (A form of temporal lobe epilepsy in which hallucinations of taste
and smell and inappropriate chewing movements are prominent features).
4- Epilepsy with generalized tonic-clonic seizures alone: (formerly known as
grand mal seizures) are a type of generalized seizure that affects the entire brain.
Tonic–clonic seizures are the seizure type most commonly associated with
epilepsy and though it is a misconception that they are the only type.
Phases: A-Tonic phase: The person will quickly lose consciousness, and the
skeletal muscles will suddenly tense, often causing the extremities to be pulled
towards the body or rigidly pushed away from it, which will cause the person to
fall if standing. The tonic phase is usually the shortest part of the seizure, usually
lasting only a few seconds. The person may also express vocalizations like a
loud scream during the tonic stage, due to air forcefully expelled from the lungs.
B-Clonic phase : The person's muscles will start to contract and relax rapidly,
causing convulsions. These may range from exaggerated twitches of the limbs to
violent shaking or vibrating of the stiffened extremities. The eyes typically roll
back and the tongue often suffers bruising by sustained strong jaw contractions.
Incontinence is seen in some cases. Due to physical and nervous exhaustion,
postictal sleep invariably follows a tonic–clonic seizure. Confusion and complete
amnesia upon regaining consciousness is usually experienced .

Febrile seizures: A febrile seizure, also known as a fever fit or febrile

convulsion, is a convulsion associated with a significant rise in body
temperature. They most commonly occur in children between the ages of 6
months and 6 years and are twice as common in boys as in girls. A febrile
seizure is the effect of a sudden rise in temperature (>39°C) rather than a fever
that has been present for a prolonged length of time.

Types of febrile seizures:

1- A simple febrile seizure is one in which the seizure lasts less than 15
minutes (usually much less than this), does not recur in 24 hours, involves
the entire body (classically a generalized tonic-clonic seizure).
2- A complex febrile seizure is characterized by longer duration, recurrence,
or focus on only part of the body.
The simple seizure represents the majority of cases. Children with febrile
convulsions are more likely to suffer from afebrile epileptic attacks in the future if
they have 1-a complex febrile seizure. 2-a family history of afebrile convulsions
in first-degree relatives (a parent or sibling), or 3- a preconvulsion history of
abnormal neurological signs or developmental delay.

Reflex epilepsy: primary reading epilepsy have seizures triggered by reading.

Photosensitive epilepsy limited to seizures triggered by flashing lights.
Precipitants can trigger an epileptic seizure in patients who otherwise would be
susceptible to spontaneous seizures. For example, children with childhood
absence epilepsy may be susceptible to hyperventilation. Other precipitants can
facilitate seizures in susceptible individuals: Emotional stress, sleep
deprivation, sleep itself, alcohol and febrile illness .
Catamenial epilepsy (CE) is when seizures cluster around certain phases of a
woman's menstrual cycle.
Pathophysiology of epilepsy: Mutations in several genes have been linked to
some types of epilepsy. Several genes that code for protein subunits of voltage-
gated and ligand-gated ion channels have been associated with forms of
generalized epilepsy and infantile seizure syndromes. E.g. mutations of the genes
that code for sodium (Na) channel proteins; these defective sodium channels stay
open for too long, thus making the neuron hyperexcitable. Glutamate, an
excitatory neurotransmitter, may, therefore, be released from these neurons in
large amounts, which triggers excessive calcium (Ca2+) release in the postsynaptic
cells. Such excessive calcium release can be neurotoxic to the affected cell.
Another possible mechanism involves mutations leading to ineffective GABA
action (the brain's most common inhibitory neurotransmitter).
Management of epilepsy: Epilepsy is usually treated with medications. Accurate
differentiation between generalized and partial seizures is especially important in
determining the appropriate treatment. In some cases the implantation of a
stimulator of the vagus nerve, or a special diet can be helpful. Neurosurgical
operations for epilepsy can be palliative, reducing the frequency or severity of
seizures; or, in some patients, an operation can be curative.
Medications: The mainstay of treatment of epilepsy is anticonvulsant
[Link] choice among anticonvulsants and their effectiveness differs by
epilepsy syndrome.
A-Sodium Channel Blockers: Sodium channel blockade is the most common
and best-characterized mechanism of currently available antiepileptic drugs
(AEDs).AEDs that target sodium channels prevent the return of the channels to
the active state by stabilizing the inactive form. So, repetitive firing of the axons
is prevented and reduces the spread of seizures. Includes: 1-
Carbamazepine(Tegretol). 2- Phenytoin (Epanutin). 3-Oxcarbazepine
(Trileptal). 4-Lamotrigine(Lamictal).
Carbamazepine (Tegretol): Carbamazepine (CBZ) is a major first-line AED for
partial seizures and generalized tonic clonic seizures. Potential dose-related
adverse effects include: dizziness, diplopia, nausea, ataxia, and blurred vision.
Rare idiosyncratic adverse effects include aplastic anemia, agranulocytosis,
thrombocytopenia, and Stevens-Johnson syndrome. Asymptomatic elevation of
liver enzymes is observed commonly during the course of therapy in 5-10% of
patients. Rarely, severe hepatotoxic effects can occur. CBZ induces the
metabolism of tricyclic antidepressants, oral contraceptives, and warfarin. CBZ
induces its own metabolism causing an increase in clearance and a decrease in
levels.
Phenytoin (Epanutin): A major first-line AED in the treatment of partial and
secondary generalized seizures in the United States. It is not indicated for
myoclonus and absence seizures. It also has an inhibiting effect on calcium
channels. The adverse-effect profile (e.g, gingival hyperplasia and coarsening of
the facial features in women) makes its use less desirable than CBZ in some
patients. Side effects include: Osteoporosis (routine screening must be performed
to detect the condition early), CNS effects occur particularly in the cerebellum
and the vestibular system causing ataxia, nystagmus and diplopia.
Oxcarbazepine (Trileptal): Oxcarbazepine (OXC) is a recently developed
analogue of CBZ. It was developed in an attempt to maintain the benefits of CBZ
while avoiding its autoinduction and drug interaction properties. OXC now is
considered a first-line therapy in some countries.
Lamotrigine (Lamictal): It has been found to inhibit depolarization of the
glutaminergic presynaptic membrane, thus inhibiting release of glutamate. The
most dangerous side effect is idiosyncratic adverse effects: skin rash, Stevens-
Johnson syndrome.
B-GABA Receptor Agonists:
Clonazepam: Clonazepam was one of the first benzodiazepines to be used for
epilepsy. It is used in the treatment of all types of myoclonus and is useful in
patients with concomitant anxiety disorder. Clonazepam has higher affinity for
the GABA-A receptor site than diazepam. It may have some action on sodium-
channel conductance.
Phenobarbital: PHB is the most commonly prescribed AED of the 20th century.
It is a very potent anticonvulsant with a broad spectrum of action. Currently, its
use is limited because of its adverse effects. It has a direct action on GABA-A. It
also reduces sodium conductance and calcium influx and depresses glutamate
excitability. The most important adverse effects of PHB are cognitive and
behavior alterations. Children are more likely than adults to exhibit behavioral
changes (e.g. paradoxical hyperkinesis). Sedation is prominent, particularly at the
beginning of therapy, and usually subsides. Psychomotor slowing, poor
concentration, depression, irritability, ataxia may occur.
C-AEDs with Potential GABA Mechanism of Action:
The enzyme glutamic acid decarboxylase (GAD) converts glutamate into
gammaaminobutyric acid (GABA). Currently, valproate (VPA) and gabapentin
(GBP) are known to have some effect on this enzyme and thereby enhance the
synthesis of GABA, VPA also blocks the neuronal sodium channel. Its
anticonvulsant effect has been attributed to 1-The blockade of voltage-dependent
sodium channels. 2-Increased brain levels of gamma-aminobutyric acid
(GABA), possibly by inhibiting GABA degradative enzymes, such as GABA
transaminase, 3-Inhibiting the re-uptake of GABA by neuronal cells. 4-enhance
the synthesis of GABA, (enhance convertion of glutamate into
gammaaminobutyric acid )
Valproate (Depakine): VPA is one of the most commonly used AEDs around
the world. It is the drug of choice for primary generalized epilepsies and is also
approved for the treatment of partial seizures. It provides excellent control in
patients with newly diagnosed typical absence seizure. It is the drug of choice for
juvenile myoclonic epilepsy and can be used in other types of myoclonus. In
addition, it is a first-line drug in photosensitive epilepsy. It is a second choice in
the treatment of infantile spasms. Dose-related adverse effects include nausea,
vomiting, tremors, sedation, confusion or irritability and weight gain, Hair loss
may occur. VPA has adverse endocrine effects, including change in sex hormone
levels causing anovulatory cycles, amenorrhea, and polycystic ovary syndrome.
Bone marrow suppression with neutropenia can occur. Acute pancreatitis is rare
but potentially fatal and usually reverses after withdrawal of VPA. The most
serious idiosyncratic adverse effect is hepatotoxicity. This is observed mainly in
patients younger than 2 years and with polytherapy.
D-Glutamate Blockers: Glutamate and aspartate are the most two important
excitatory neurotransmitters in the brain. Topiramate (Topamax):
Topiramate is a very potent anticonvulsant. Topiramate has multiple mechanisms
of action: It exerts an inhibitory effect on sodium conductance, enhances GABA
by unknown mechanisms, and inhibits glutamate receptor.
E- AEDs with Other Mechanisms of Action:
Levetiracetam (Keppra): The mechanism of action is possibly related to a brain-
specific stereo-selective binding site, synaptic vesicle protein 2A (SV2A). SV2A
appears to be important for the availability of calcium-dependent neurotransmitter
vesicles ready to release their content. LEV inhibits Ca 2+ release from the
sensitive stores without reducing Ca2+ storage, which could explain some of
LEV’s antiepileptic properties.
Epilepsy surgery:
Epilepsy surgery is an option for patients whose seizures remain resistant to
treatment with anticonvulsant medications who also have symptomatic
localization-related epilepsy; a focal abnormality that can be located and
therefore removed. The evaluation for epilepsy surgery is designed to locate the
"epileptic focus" (the location of the epileptic abnormality) and to determine if
resective surgery will affect normal brain function. Physicians will also confirm
the diagnosis of epilepsy to make sure that spells arise from epilepsy (as opposed
to non-epileptic seizures). The evaluation typically includes neurological
examination, routine EEG, Long-term video-EEG monitoring, and neuroimaging
such as MRI. The most common surgeries are the resection of lesions like tumors
or arteriovenous malformations, which, in the process of treating the underlying
lesion, often result in control of epileptic seizures caused by these lesions. The
most common form of intractable epilepsy in these disorders in adults is temporal
lobe epilepsy with hippocampal sclerosis, and the most common type of epilepsy
surgery is the anterior temporal lobectomy, or the removal of the front portion of
the temporal lobe including the amygdala and hippocampus. Some neurosurgeons
recommend selective amygdalahippocampectomy because of possible benefits in
postoperative memory or language function.

Differential diagnosis of epilepsy:

1- syncope.
2- psychogenic attacks.
3- sleep disorders.
4- movement disorders.
5-transient ischemic attacks.
6- migraine.
7- transient global amnesia.
8- metabolic disorders.
 EPILEPSY EMERGENCIES
Status Epilepticus

Introduction:

It has a high morbidity and mortality. Status epilepticus is a manifestation of a disease so it is

mandatory to look for an underlying cause. Prolonged seizures causes higher rate of
complications including permanent neuronal damage.
Definitions:

A-Status epilepticus: Seizure that is prolonged after initiation of mechanisms to terminate the
seizure within 5 minutes.

B- Refractory status epilepticus: SE that persists despite adequate administration of

benzodiazepines and at least one antiepileptic drug.

Forms of status epilepticus:

A- Convulsive status epilepticus: repeated generalized tonic clonic seizures with persistent
postictal depression of neurologic function between seizures.

B- Nonconvulsive status epilepticus: seizures produce a continuous or fluctuating “epileptic

twilight” state.

C- Repeated partial seizures: focal motor signs, focal sensory symptoms, or focal impairment
of function (e.g aphasia) not associated with altered awareness (epilepsia partialis continua).

Causes of status epilepticus:

1- vascular: stroke, subarachnoid hemorrhage, epidural or subdural hemorrhage, intracerebral

hematoma or vasculitis.

2- infectious: meningitis, encephalitis or brain abscess.

3-toxic: cocaine, tricylic antidepressants, anticholenergics, isoniazid or withdrawl of

sedatives.

4- metabolic: hyponatremia, hypoglycemia, hypocalcemia or hypomagnesemia.

5- Others: tumors and eclampsia.

Management : Initial stabilization : Oxygenation and ventilation, IV access, Antiepileptic

adminesteration, Glucocheck, Diagnostic studies, administration of Thiamine, 100 mg for
alcohol abuse pt.
Laboratory studies: Serum electrolytes (Ca, Mg, Na), Glucose, Renal and Liver function
testing , Antiepileptic drug levels, Toxicology screen

Neuroimaging: A noncontrast Brain CT should be considered for all SE patients once they
have been stabilized.
Lumbar puncture: if you suspect CNS infection give empiric antibiotic or antiviral therapy
and obtain CT brain before lumbar puncture.

EEG monitoring: for nonconvulsive SE, Comatose patient after generalized seizure or with
use of paralytics where neurological examination is impossible.
Drugs:

A- Benzodiazepines: The first drugs of choice for SE, includes:

1- Diazepam (0.2 mg/kg given at 5 mg/min).

2-Lorazepam (0.1 mg/kg given at 2-4 mg/min). Seizure activity terminated in 60% of the
lorazepam-treated patients, 43% of diazepam-treated patients and 21% of patients who
received placebo. When IV access is not available alternative routes must be considered.
Both diazepam and lorazepam can be given rectally.
B- Phenytoin: Dose: 20 mg/kg in a nonglucose solution, with a second dose of 10 mg/kg
given if needed with target level: 15–20 mg/L.

C- Fosphenytoin: a prodrug of phenytoin, has phosphoryl group which makes it water soluble
with lower pH and Can be infused faster than phenytoin.
D- Valproate: Excellent safety profile, loading dose of 15 to 20 mg/kg in dextrose-containing
solutions at a rate of 3 to 6 mg/kg/min and target levels: 75–100 mg/L
E- Phenobarbital: It works on (GABAA) receptor, similar to benzodiazepines.
F- Levetiracetam.

Refractory status epilepticus treatment: Current literature supports the use of continuous
IV infusion of anesthetic doses of midazolam, barbiturate or propofol.

Morbidity of status epilepticus is related to: Cerebral hypoxia, direct neuronal death and
systemic effects such as: hypoxia, hypoperfusion , metabolic acidosis, hyperthermia,
rhabdomyolysis and hypoglycemia.
 Approach to Myopathy
Essentials for diagnosis

Weakness, generally more proximal than distal

Skeletal muscles generally affected

Normal sensations

Normal sphincter function

Relative preservation of deep tendon reflexes

Positive laboratory tests to support the diagnosis

Electromyography is essential tool of diagnosis

Muscle biopsy and genetic testing offer definitive diagnosis.

Classification of myopathies

Hereditary:

•Congenital myopathies

•Muscular dystrophies

•Myotonias

•Channelopathies

•Metabolic myopathies

•Mitochondrial myopathies

Acquired:

•Inflammatory/ immune-mediated myopathies

•Drug induced / Toxic myopathies

•Myopathies due to systemic illness

•Endocrine myopathies

•Infectious myopathies

Acquired Inflammatory myopathies

Polymyositis

Dermatomyositis

Sarcoid myopathy

Infectious myopathy.
Polymyositis

Myopathic distribution of weakness

Age at onset: any age

Muscle pains and tenderness

Spontaneous EMG activity

Elevated CK level

Presence of myositis antibodies

Muscle biopsy; endomesial infiltration of inflammatory cells.

Dermatomyositis

Myopathic distribution of weakness

Age at onset any age

Muscle pains and tenderness

Characteristic skin lesions

Markedly elevated CK level

Presence of myositis antibodies

Muscle biopsy; perivascular and peri-mesial infiltration of inflammatory cells

Infectious myopathies

Viral myositis; influenza, enteroviruses, retroviruses, HIVassociated myopathy (fever, myalgias and
weakness, highly elevated CK, myoglobinuria, may be renal failure).

Bacterial myositis; may occur in DM, IV drug abusers, malignancy, muscle trauma, present by fever,
myalgias, focal or severe muscle weakness, elevated CK.

Parasitic myositis; fever, myalgias and proximal weakness, elevated CK, eosinophilia in CBC.

Drug induced / Toxic myopathies

Corticosteroid induced myopathy

Cholesterol lowering agent myopathy

Myopathy in critical illness seen in ICU.

Secondary Metabolic / Endocrinal myopathies

Hypokalemic myopathy; weakness myalgia, k<3meq/L. diuretics induced

Chronic renal failure related myopathy

Hypothyroid myopathy; proximal muscle weakness, pseudo hypertrophy, deposition of myxedema

tissue in muscles.

Hyperthyroid myopathy; proximal muscle weakness, atrophy, exaggerated deep tendon jerks.

Hyper parathyroid myopathy; proximal muscle weakness, atrophy, respiratory failure, exaggerated deep
tendon jerks.

Vitamin D related myopathy; progressive proximal muscle weakness, myalgias, low serum Vit D level.

Cushing disease; truncal obesity, acne, hypertension, myopathy

Treatment of acquired myopathies

Auto-immune inflammatory myopathy: corticosteroids, plasma pheresis, IVIGs.

Metabolic: correction of metabolic changes.

Endocrine: correction of hormonal abnormalities

Infectious: anti-bacterial, anti-viral

Toxic and drug induced: discontinuation of the cause.

Hereditary myopathies

Primary metabolic myopathies (caused by biochemical defect of skeletal muscle energy system as
defects in carbohydrate metabolism, lipid metabolism)

Mitochondrial myopathies (due to defects in the respiratory chain)

Channelopathies (hypokalemic periodic paralysis, hyperkalemic periodic paralysis, myotonia congenita,

myotonic dystrophy) (Clinical

myotonia; failure of immediate muscle relaxation after contraction has stopped, or delayed muscles
relaxation, by voluntary muscle contraction or by hammer testing)

Muscular dystrophies (hereditary slowly progressive myopathy with specific histologic abnormalities;
severe fibrosis, proliferation of fatty and connective tissue)

Duchenne Muscular Dystrophy

It is an x-linked recessive inherited

Typically affect males

Onset before age of 5

Proximal muscle weakness

Positive Gower`s sign

Calf muscle pseudo hypertrophy

Elevated CK level (10 folds increase)

Severely reduced or absent dystrophin in muscle biopsy

Duchenne Muscular Dystrophy DMD

Typical course of DMD; delayed walking, frequent falls, difficulty climbing stairs, getting up from the
floor or running (Gower`s sign).

By school age, the child may have a waddling and unsteady gait.
To try to keep his balance, he sticks his belly out and puts his shoulders back. He later has difficulty
raising his arms.

Many children with DMD lose the ability to walk some time between ages 7 and 12.

In the teen years, activities involving the arms, legs or trunk may require assistance or mechanical
support.

Becker Muscular Dystrophy

It is an x-linked recessive inherited

Typically affect males

Onset after age of 12

Normal milestones of development

Proximal muscle weakness

Positive Gower`s sign

Calf muscle pseudo hypertrophy

Elevated CK level (at least 5 folds increase)

Decreased or abnormal structure of dystrophin in muscle biopsy

Myasthenia gravis

In most of cases there are auto-antibodies to Acetyl Choline receptors.

Myasthenia gravis

An autoimmune neuromuscular disorder that causes weakness in the skeletal muscles

It occurs due to impaired communication between nerve cells and muscles at the myoneural junction,
that prevents muscle contractions.

The muscles most affected are, extra ocular, bulbar, of breathing, as well as facial and shoulder followed
by pelvic muscles, neck muscles usually spared.
The weakness tends to temporarily worsen with activity and improve with rest, with the typical easy
fatiguability.

Females are more affected than males.

Diagnosis

Medical and neurologic evaluation

Blood tests to check for antibodies (serum anti-acetyl choline receptor antibodies)

Imaging scans for thymus gland by mediastinal CT scan.

Electrical tests of nerve and muscle function (electromyography; single fiber EMG, and nerve
conduction studies, with decrement study).

Treatment

Medications

Drugs to suppress the immune system and decrease the autoantibodies as steroids and
immunosuppressants.

Drugs that slow the breakdown of acetylcholine and prolong its action at the nerve-muscle connection;
Ach re-uptake inhibitor; pyridostigmine.

Surgery: The thymus gland should be removed if the thymus is enlarged.

Plasma exchange: In plasma exchange, abnormal antibodies are removed from the blood. Antibody
removal in this way produces temporary improvement in majority of patients but also requires some
form of immune suppression so that the antibodies do not rebound.

Intravenous immunoglobulin (IVIG):These temporarily modify the immune system.

 Approach to Neuropathy
What is the lower motor neuron system

Anterior horn cells.

Roots.

Peripheral nerves.

Myoneural junction.

Muscles.

What is a nerve

A nerve or a peripheral nerve is the part of the lower motor system that starts from the anterior horn cell,
root, plexus and peripheral nerve proper.

Nerves are cranial (12) and spinal (31)

Nerves are heavily myelinated, thinly myelinated and unmyelinated

Nerve structure

The nerve basic functions are based on 3 components; myeline sheath, axon and vasa nervosum

Myelin allows for insulation and rapid conduction of nerve impulses. Lesion causes demyelination
neuropathy.

Axons are the actual nerve “wires” that conduct the electrical signals. Lesion causes axonal neuropathy.

Blood vessels (vasa nervosa) carry nutrients to the nerves and waste products away from them. Lesion
causes axonal neuropathy.

Symptoms and Signs of Neuropathy

Sensory symptoms

Positive symptoms: tingling, pins and needles, abnormal pain

Negative symptoms: numbness, sensory loss

Motor symptoms

Positive symptoms : fasciculations

 Negative symptoms: weakness, hypotonia, gait abnormalities

Autonomic dysfunction: skin dryness, loss of sweating, loss of hair

Distribution

In peripheral neuropathy: bilateral , symmetrical, distal more than proximal

In root lesion: dermatome and myotome distribution

Where is the lesion in neuropathy

Mononeuropathy.

Mononeuropathy multiplex.

Polyneuropathy.

Where and What is the lesion in mononeuropathy ?

Acute:

Bell`s palsy: cold exposure induced, head or facial surgery

Trauma: fracture long bones

Cut injuries: glass, sharp objects.

Diabetes mellitus (DM): vascular ischemia; facial, abducent and oculomotor nerves.

Chronic (nerve entrapment):

Median nerve at the wrist (carpal tunnel syndrome)

Ulnar nerve at the elbow (cubital syndrome)

Lateral cutaneous nerve at the inguinal ligament

Where and What is the lesion in mononeuropathy multiplex ?

Acute:

Diabetes mellitus.

Multifocal motor neuropathy

Vasculitis

Chronic:
Sarcoidosis.

Leprosy.

HIV.

Where and What is the lesion in polyneuropathy ?

Acute:

Diabetes mellitus.

Guillain Barre syndrome.

Chronic:

Diabetes mellitus.

Paraneoplastic syndrome.

Chemotherapy.

Vit B12 deficiency, alcoholism.

Systemic / Endocrinal causes of polyneuropathy

Hereditary polyneuropathy; sensory-motor (CMT), pure sensory, and sensory-autonomic types.

Diabetic Neuropathies

1-Diabetic polyneuropathy:

[Link] sensorimotor

[Link]

2-Diabetic proximal neuropathy(Diapetic Amyptrophy)

3-Mononeuropathy: cranial or peripheral nerves

4-Trunkal neuropathy

Diabetic peripheral neuropathy

With long lasting DM, poor control.

Mainly sensory, in LLs then Uls.

Marked pain and parasthesia.

Glove and stock hyposthesia.

Deep sensory loss causing sensory ataxia.

Marked trophic changes.

Investigations

1-NCS: axonal affection of sensory nerves and lately of motor nerves.

2-EMG: chronic denervation of distal muscles.

3-Nerve biopsy: axonal loss and thickened epineural arterioles.

Treatment of Diepetic Neuropathy

1-Good glycemic control.

2-Pain treated by:

a-Antidepressan: TCA, SNRI, SSRI

B-Anticonvulsant: Gabapentin, pregabalin, carbamzapine

Guillain-Barre syndrome (GBS)

Autoimmune disease attaching nerve roots and peripheral nerves.

It is the commonest cause of acute flaccid paralysis.

The classic presentation is characterized by an acute monophasic, non-febrile, postinfectious illness

manifesting as mixed motor (proximal) ascending weakness, sensory and autonomic polyneuropathy,
also may be bilateral facial LMNL and areflexia.

Pathophysiology

Roughly two thirds of patients have a history of an antecedent gastrointestinal or respiratory tract
infection.

Some of the pathogenic triggers of GBS include Epstein-Barr virus, cytomegalovirus, enteroviruses,
hepatitis A and B, varicella, Mycoplasma pneumoniae, and Campylobacter jejuni, which is the most
common.

Resemblance of the triggering pathogens to antigens on peripheral nerves (ie, molecular mimicry) leads
to an autoimmune response mounted by T-lymphocytes and macrophages.

Subtypes of GBS

GBS peripheral nerve damage can be classified histopathological into 2 main types: demyelinating
forms and axonal forms.

GBS was subdivided into 4 distinct forms based on histopathological and neurophysiological basis:

Acute inflammatory demyelinating polyradiculoneuropathy (AIDP),

Acute motor axonal neuropathy (AMAN),

Acute motor and sensory axonal neuropathy (AMSAN),

Miller-Fisher syndrome (MFS).

Acute inflammatory demyelinating polyradiculoneuropathy (AIDP)

This accounts for 80-90% of GBS cases.

It is an immune-mediated attack of myelin with infiltration of lymphocytes and macrophages with

segmental demyelination.

Motor and sensory fibers are usually affected simultaneously, producing corresponding deficits.

Acute motor axonal neuropathy (AMAN)

This form of neuropathy is the most seen in China and Japan (50-60% of cases), as apposed to other
countries (10-20% of cases).

In this form, axonal degeneration occurs by immune attack within 1-2 weeks after infection

C jejuni the most common preceding infection, and antiganglioside antibodies are usually found in this
type.

Miller-Fisher syndrome (MFS)

The involvement of CNs is very distinct in this form of GBS.

Ocular motor nerves (oculomotor, trochlear, and abducens) are affected and produce a triad of
ophthalmoplegia, ataxia, and areflexia.

The characteristic autoantibodies are against gangliosides GQ1b.

Clinical picture of AIDP

An ascending motor weakness is noted along with areflexia in the classic form.

Bilateral facial palsy are more frequent cranial nerves involved with this syndrome.

Lower limb weakness is usually noticed first. Later, trunk muscles and upper extremities show
involvement.

Weakness also may involve the respiratory muscles, and some patients need respiratory support during
the course of the disease, and mechanical ventilation is used until respiratory muscle function returns

The autonomic neuropathy manifestations include orthostatic hypotension, hypertension, pupillary

dysfunction, sweating abnormalities, and sinus tachycardia.

Diagnosis

Based on progressive ascending weakness with areflexia.

Lumbar puncture findings are suggestive of demyelination (ie, increased protein >45 mg/dl within 3
weeks of onset) without evidence of active infection (lack of CSF pleocytosis; greater than 50
mononuclear cells/mL of CSF makes the diagnosis of GBS doubtful).

Electrodiagnostic studies reveal the following:

Reduced conduction velocity of motor and sensory nerves

Prolonged, or absent F response (88%)

Increased distal latencies (75%)

Criteria for axonal forms include decreased amplitude of motor unit potentials

Treatment

Plasmapheresis is started immediately once suspected GBS.

Intravenous immunoglobulin (IVIG) is the most effective form of therapy in pediatrics and used as a
second line of treatment after poor response of plasmapheresis in adults.

Corticosteroids were previously used to treat GBS, but current data indicate they provide little benefit.

Physiotherapy.

Approach to a patient with neuropathy

Proper history and examination to diagnose; mono or polyneuropathy or other types.

Diagnose the possible cause; autoimmune, metabolic, toxic, drug induced or other causes.

Initial evaluation of a patient with neuropathy should include a complete blood count, comprehensive
metabolic profile, and measurement of ESR, FBS, vit B12, and TSH.

Electrodiagnostic studies are recommended if symptoms persist and if the diagnosis remains unclear
after initial diagnostic testing and a careful history and physical examination.
 Parkinson Disease
A. Description:
Parkinson’s disease (PD) is a neurodegenerative disease caused by a depletion of dopamine-producing
cells in the substantia nigra. The cardinal features of PD are a resting tremor, rigidity, bradykinesia, and
diminished postural stability.
Parkinsonism: These are Parkinson-like syndromes, , that initially present as PD but are differentiated
from idiopathic PD on the basis of history & examination and progression of the disease & causative
etiology.

Epidemiology
1. Incidence: . Estimates range from 4.9 to 25.6 per 100,000 population.

2. Prevalence: Estimates are that 1.5 million Americans have PD, with approximately 50,000 new
cases diagnosed each year.
a. Age: The average age of onset is about 60 years.
b. Gender: The prevalence is slightly higher in males.

c. Race: The prevalence is slightly higher in whites.

CLINICAL PRESENTATION

The four primary signs of PD

→bradykinesia, tremor, rigidity, and gait disturbance .
At least two of these four features are needed for diagnosis.
Non-Motor Symptoms: usually late in the course of PD
Autonomic dysfunction,
cognitive/ neurobehavioral abnormalities,
sleep disorders and

sensory abnormalities such as anosmia, paresthesias and pain

Bradykinesia , “Slow Movement”

Actually, not only slow but a diminution in amplitude of voluntary movements or reduction in
“automatic” movements

The most disabling PD symptom, is a decreased ability to initiate movement (akinesia is the extreme
manifestation).
 This may affect multiple functions, particularly fine motor tasks such as buttoning a shirt or
handwriting, the latter becoming micrographic.

Decrease in “automatic” movements

Arm swing ambulating
Facial expression: hypomimia
Swallowing: sialorrhea
Decreased eye blink; Impaired gaze and eyelid opening
Progressively diminishing amplitude of voluntary movements;

Asymmetry typical
Micrographia
Hypokinetic dysarthria (voice trails off)
Tasks take longer (eating, getting dressed, etc.)

Rigidity
It is a resistance to passive movement throughout the entire range of motion occurring in flexor
and extensor muscles. This contrasts with spasticity, wherein there is an initial marked resistance to
passive movement and then a sudden release, for example, clasp-knife phenomena.

The classic cogwheel quality (stop-and-go effect) is from a tremor superimposed on the
altered muscle tone. Very early on, patients are often concerned about stiffness, “weakness,” or fatigue.
Initially, the patient will just note a limitation in their daily activities or exercise capacity—unable to
hike as long a distance, inability to get to the ball when playing tennis, or simply walking from the
car to the store.
Pain in the shoulder & back muscles are the outcome of regidity & could be

the source of miss-diagnosis of disc pathology in old people.

Facial expression
Other individuals may present with a masked facies non-emotional, bland, and expressionless,
which later on becomes associated with ↓ blink frequency, excessive sweeting with drooling of
saliva .
The Myerson’s sign, or glabellar tap sign, is elicited by having the patient look straight ahead while
the examiner gently taps with her or his index finger tip between the medial ends of the eye-brows.

Tremor
It occurs in 75% of patients. Typically,
it is prominent at rest, having a frequency
of 3–7 Hz. Although this tremor usually does
not significantly interfere with activities of daily living (ADLs), such as eating or writing, the
patient finds it very embarrassing.
PD patients frequently sit in the physician’s office placing the affected hand out of sight down
by their side or underneath a jacket.

Speech
Slow mono-tonus speech loss of intonation
Tachy-phemia
Sudden rush of uni-ntellagable speech mirror image anteropullsion

Shuffling GAIT
The gait
Reduction in stride with one leg sticky to the ground
with decreased arm swing, stooped posture, and en bloc turning,

FEST ITINANT GAIT

Postural instability, usually present at later stages of PD characterized by a change in the center of
gravity typified by falling forward (propulsion) or backward (retropulsion) and a festinating (short
+ fast)
Freezing of Gait (FOG)= gait bradykinesia (GB)
start hesitation
turning hesitation
narrow spaces

Turning in bed
At first; the patient should sit in bed first then push himself toward the side he would like to move
Later he is in need for someone to help him to turn in bed

Non-motor features of Parkinson’s disease

Secondary features
Later in its course, certain secondary features often occur .
Cognitive Symptoms
Behavioral/Neuropsychiatric Changes
Autonomic Nervous System Failure
Sleep Disturbances
Sensory disturbances

Pain
Paresthesiae numbness burning akathisia restless legs syndrome
Fatigue

Cognitive Symptoms
Subtle neuropsychological changes that are difficult to assess in a typical primary
care encounter are often evident early in the course of PD.

The executive functions— ability in "set-switching,"

problem-solving strategies,
concept formation,
attention capacities,
decision making and
effective use of working memory—

They are the first and most severely affected cognitive domains.
Clinically, executive function deficits can be expressed as difficulties with everyday activities such
as organizing medications, paying bills, and losing productivity.

Impairment in visuo-spatial function

Also is an early cognitive outcome of PD, although often it is detected only with specific
neuropsychological testing such as a complex figure copy or facial recognition test.
Memory deficits are seen mainly as the illness progresses. Clinically, these deficits manifest as
retrieval deficits rather than disturbances in immediate recall, suggesting that unlike Alzheimer disease
(AD), encoding processes are not disrupted
Autonomic Nervous System Failure

These include
orthostatic hypotension, constipation, urinary frequency and urgency, erectile dysfunction and
vaginal tightness, and sweating abnormalities
 impaired gastrointestinal motility impairement, thermoregulation disorders
Dysphagia is usually present later on in the PD patient. This relates to the development of
oropharyngeal and esophageal motility disorders.
Sleep Disturbances
Sleep disturbances are common in PD, but their cause is unclear.
In one study, 42% of individuals with PD had sleep problems compared with
12% of controls.
Specific symptoms included

Insomnia in 32%, RBD in 32%, and Excessive daytime sleepiness in 15%

Restless Leg syndrome.
Depletion of dopamine has been hypothesized as one process that promotes disrupted sleep in people
with PD.

Prognosis
The clinical course of PD is quite variable. However, it usually progresses slowly and inexorably
Typically, the illness begins unilaterally with focal tremor or difficulty using
one limb. Eventually, the symptoms become more generalized and occur on the
contralateral side, interfering with activities of daily living.

More rapid rates of change

in patient with early cognitive problems,
older age, and
lack of tremor at onset .

Age at onset .
Those with late-onset PD had a 3.8% annual rate of decline, whereas the
Several secondary signs of parkinsonism also develop as previously noted

Rate for those with early-onset was 2.4%

Diagnostics:
The diagnosis is clinical .
1. History
 Unilateral onset,
Bradykinesia
Regidity
Postural instability

tremor.
2. Physical examination:
Focuses on the motor system—the presence of tremor, rigidity, impaired balance,
gait abnormalities, and diminished arm swing.

[Link] red flag

[Link] response on L-dopa

[Link] course
[Link] other explanation.
Exclusion Criteria for Diagnosis of Parkinson Disease
Red flag
Identifiable causes( Secondary parkinsonism )
Parkinsonism due to identifiable causes, such as stroke, Head injury,

encephalitis, neuroleptic exposure, Hydrocephalus, or brain tumor

ANY OF THE FOLLOWING ( Atypical PD )

Supranuclear gaze palsy
Cerebellar signs
Autonomic insufficiency, early and severe, particularly orthostatic hypotension
Medication resistance, poor response to large doses of levodopa

Sustained remissions
Oculogyric crises

Imaging
Use of CT and MRI
sometimes helps to distinguish idiopathic PD from other forms of parkinsonism.
 atherosclerotic brain disease or normal-pressure hydrocephalus and
rarely demonstrate a structural lesion.
MRI sometimes shows signs typical for multiple-system atrophy (putaminal
atrophy, hot cross bun sign, a hyperintense putaminal rim, and infratentorial signal changes)

Medications
Levodopa is the gold standard for the treatment of PD
No medical or surgical therapy has been shown to provide superior anti-parkinsonian benefits than can
be achieved with levodopa.

However, chronic levodopa treatment is associated with the development of motor complications and
non-motor complications in the majority of patients
Unfortunately, it is not still how levodopa should be administered in the early stage (dose, formulation,
interval between doses) in order to minimize the risk of complications.
Indeed, several studies have now shown that continuous infusion of levodopa, which provides a more
continuous dopaminergic stimulation in PD patients who experience motor complications, is associated
with a reduction in both off time and dyskinesia.
Accordingly, there has been a search for an oral levodopa treatment strategy that might mirror the
pharmacokinetics of a levodopa infusion and provide the benefits of the medication without motor
complications.
Carbidopa inhibits the decarboxylation of levodopa to dopamine in the systemic circulation, allowing
for greater levodopa distribution into the central nervous system.
Entacapone is an inhibitor of catechol-O-methyl transferase (COMT) that extends the elimination half-
life of levodopa , and thus has the potential to provide more continuous availability of levodopa

When entacapone is given in conjunction with levodopa and carbidopa, plasma levels of levodopa are
higher and more sustained than after administration of levodopa and carbidopa alone.
Levodopa/carbidopa/entacapone is useful in advanced Parkinson disease in patients with motor
fluctuations.
In the STRIDEPD (STalevo Reduction In Dyskinesia Evaluation) study, patients with early Parkinson
disease treated with levodopa/carbidopa/entacapone (Stalevo) developed more dyskinesia than patients
treated with levodopa/carbidopa; therefore, levodopa/carbidopa/entacapone is not recommended for
treatment of early disease.

Levodopa provides the greatest antiparkinsonian benefit for motor signs and symptoms, with the fewest
adverse effects in the short term; however, its long-term use is associated with the development of motor
fluctuations (“wearing-off”) and dyskinesias.
Once fluctuations and dyskinesias become problematic, they are difficult to resolve.
 Hyperkinesias
Criteria of Hyperkinesias
• Regular vs irregular
• Rhythmic vs. arrhythmic
• Sustained vs. Nonsustained- Paroxysmal vs. Nonparoxysmal
• Slow vs. fast

• Amplitude
• At rest vs. action
• Patterned vs. non-patterned
• Combination of varieties of movements
• Supressibility, purposeful or semi
Definitions

• Chorea: derived from the Greek word “to dance” to describe the arrhythmic, involuntary flitting
movements
• Athethosis: involuntary writhing movements

• Hemiballism: large amplitude involuntary movement restricted to one side of the body; usually
involves proximal upper limb.

• Myoclonus: sudden brief jerk or shock-like movements

• Dystonia: abnormal sustained posture resulting from simultaneous co-contraction of agonist and
antagonist muscles.

• Tremor: rhythmic oscillation of a body part due to alternating or synchronous contractions of

opposing muscles
• Tics: sudden, brief, purposeless, stereotyped simple or complex movements or vocalizations
• Akathisia: inner restlessness; often associated with external signs of restless behavior

Chorea
• Irregular rapid, low amplitude, brief movements of extremities & face.
• Semi purposeful or apparently purposeful.
• ± Facial grimacing, eyebrow movement and respiratory noises.

• Increase by stress and decrease by sleep.

 • ± Athetosis (slower, distal, writhing and sinuous).

• Motor impersistence: difficulty sustaining ongoing movement e.g. inability to maintain forced
eye closure, or protrude the tongue for long periods.

Special Signs
1. Tongue sign: patient cannot keep his tongue protruded outside mouth.

2. Boat hands or scaphoid hands

3. Pronator signs.
4. dancing gait.

Causes of Choreic Syndromes

GENETIC CHOREAS
Huntington’s disease (AD).

Huntington’s disease-like 2 (AD).

Dentatorubropallidoluysian atrophy (DRPLA)
Neuroacanthocytosis
Ataxia teleangiectasia
Benign hereditary chorea (AD)
Paroxysmal kinesigenic choreoathetosis

AQUIRED CHOREAS (non-genetic)

1. Structural basal-ganglia lesions: stroke
2. Parainfectious & autoimmune disorders: Sydenham’s chorea, SLE.

3. Infectious chorea
4. Metabolic or toxic encephalopathies
5. Drug induced
6. Functional forms.

Huntington’s Disease
AD causing choreic and mental changes.
Caused by unstable trinucleotide CAG repeat expansion in chromosome 4p, HTT gene, which encodes
a protein (Huntingtin) widely expressed in neuronal and other tissues.
Age: 30 – 55 years around 40 years.
< 20 years → juvenile HD (Westphal variant) 5 %.
>60 years → elderly onset disease 25%.
Gradual, progressive, 2/3 starts by motor symptom (chorea).

1/3 starts with personality and cognitive changes.

-Motor:
Chorea
Parkinsonism
Dystonia
Myoclonus

Motor impersistence
Gait disorder
-Psychiatric:
Personality
Affective; depression
Obsessive compulsive

Psychosis (rare)
-Cognitive:
Executive dysfunction
Dementia

Sydenham's Chorea (Rheumatic chorea)

• Due to preceding infection by group A β-haemolytic streptococci→ immunological cross
reaction (molecular mimicry).
• 5-15 (8-9) years old.

Clinical Picture: female: male (2:1).

• Abrupt or subacute chorea and regressive.
• Hypotonia, pendular knee jerk, dysarthria.

• Tics may also occur, migraine

 • Emotional & behavioral abnormalities, dysexecutive syndrome
• May be unilateral (20%) ± hemiballsim, ± residual or recurrent chorea.

• In a study, all patients with active SC have antibasal ganglia antibodies demonstrated by ELISA

Workup of Chorea
1. Routine blood work, Thyroid studies, ESR, ANA, antiphospholipid antibodies, ASO titers…
2. Test for thyroid function, renal and liver function, electrolytes, erythrocyte sedimentation rate,
antinuclear antibodies, anti double-stranded DNA antibodies, ↑↑ CPK, anticardiolipin antibodies,
and lupus anticoagulant.

3. Test for acanthocytes in peripheral fresh blood film. perform three assays.
4. Perform brain MRI.
5. Genetic test: for Huntington disease. If the latter genetic test is negative, consider
spinocerebellar ataxia type 17 and C9orf72 in white individuals, and Huntington disease-like
syndrome type 2 in subjects with black African ancestry.

Treatment of Chorea
• Treat underlying acquired cause: autoimmune, WD.

• No protective treatment

• Symptomatic treatment of chorea:

1. Dopamine receptor blockade

• Typical neuroleptics—caution!

• “Atypical” neuroleptics: tiapride, olanzapine, and risperidone Presynaptic

dopamine depletion: Tetrabenazine 25-100 mg/day, deutetrabenazine (HD),
valbenazine (tardive dyskinesia)
2. Glutamate antagonism: Amantadine
3. GABA-ergic: Valproic acid.

4. Treat associated symptoms: psychiatric, seizures

5. Botulinum toxin, DBS for certain cases

Tic Disorders
Definition: Rapid, non-rhythmic, stereotyped involuntary movements usually affecting the face, head, or
UL.
• More semi purposeful, which may be:
 • Simple or complex, motor or vocal.
• Acute, subacute or chronic.
• Brief or sustained "dystonic tics.”

• Motor tics:
• Simple motor tics: blinking, head jerking, shrugging shoulder, grimacing.
• Complex motor tics; picking at the body or object, gestures, rubbing or manipulative movements.
• Vocal tics: simple (noises, cough, sniffs) or complex (words, phrases).
Waxing and waning, transient remissions.
Persist during sleep (all stages)
• Copopraxia = a sudden, tic-like vulgar, sexual, or obscene gesture

• Echopraxia = a mirror phenomena, such as involuntary, spontaneous imitation of someone else’s

movements
• All are considered complex vocal tics
• Palilalia = repeating one’s own sounds or words
• Echolalia = repeating the last heard sound, word, or phrase

• Coprolalia = the sudden, inappropriate expression of a socially unacceptable word or phrase

Tourette's Syndrome
DSM-IV Diagnostic Criteria

• Both multiple motor and one or more vocal tics have been present at some time during the
illness, although not necessarily concurrently.
• The tics occur many times a day (usually in bouts) nearly every day or intermittently throughout
a period of more than 1 year, and during this period there was never a tic-free period of more
than 3 consecutive months.
• The onset is before age 18 years.

• The disturbance is not due to the direct physiological effects of a substance (e.g., stimulants) or a
general medical condition (e.g., Huntington’s disease or postviral encephalitis).

Treatment of Tic Disorders

1. Education; Patient, family, and school
2. Counseling for family and patient
3. Relaxation therapy
 4. Supportive therapy
5. Habit Reversal Therapy
6. Pharmacological: α-2 agonists (Clonidine), neuroleptics
7. Treatment of comorbidities.

TREMORS
Tremor is an involuntary, rhythmic, oscillatory movement of a body part

Aetiology
1. Essential tremor
2. Parkinsonian tremor
3. Dystonic tremor

4. Holmes tremor
5. Cerebellar tremor
6. Orthostatic tremor
7. Functional tremor
8. Enhanced physiological tremor
9. Neuropathic tremor

Essential Tremor (ET):

Sporadic or familial AD, insidious, and progressive.
Bimodal onset; late adolescence and older adulthood.
Mixture of kinetic and (>) postural tremor, 4 -12 hz.
Bilateral roughly symmetric or mild asymmetric.
Start in UL (95%), head, face, voice….

± mild intentional component, ± mild gait ataxia.

No other neurological deficits (except Froment's sign).
Isolated focal or task specific (vs. dystonic).

Treatment of ET
1. Propranolol (up to 320 mg/day), and other B blockers.
 2. Primidone (up to 250 mg three times daily).
3. Gabapentin (1200 to 3600 mg/day), and topiramate.
4. Mirtazapine, alprazolam, Phenobarbital, Clonazepam
5. Botulinum toxin for task-specific, severe isolated head, or dystonic tremors.

6. Wearing wrist weights while eating, drinking from a heavier mug, using a fat pen rather than a
thin one, and using heavier utensils
7. Surgical: Vim thalamotomy or Vim DBS.

MYOCLONUS
The essential feature is the sudden, brief, and shock-like movement.
Positive Myoclonus: muscle contractions.
Negative Myoclonus; interruptions of tonic muscle activity = asterixis= flapping tremor.
Treatement: piracetam, levetiracetam, valproic acid and clonazepam

Causes of Myoclonus
Generalised Myoclonus:
a) Essential myoclonus: Non-progressive condition in which myoclonus is only or most important
neurological symptom and sign.

b) Progressive myoclonic encephalopathies (PME):

 Myoclonus (with or without seizures) is part of a progressive encephalopathy.

e.g., mitochondrial encephalomyopathy (esp. MERFF); Creutzfeldt–Jacob disease, Alzheimer’s disease;

and Metabolic myoclonus (e.g. uraemia, hepatic failure,
a) Static myoclonic encephalopathies: obvious myoclonus occurs after some acute and now static
cerebral insult, e.g. postanoxic action myoclonus (Lance–Adams syndrome).
b) Myoclonic epilepsies: epilepsy is the main problem, but myoclonus is present.
Focal Myoclonus: myoclonus is restricted to one small discrete part of the body. → Spinal myoclonus,
Hemifacial spasm.

Dystonia:
• It is a movement disorder characterized by sustained or intermittent muscle contractions causing
abnormal, often repetitive, movements, postures, or both.
• Dystonic movements are typically patterned, twisting, and may be tremulous.
 • Dystonia is often initiated or worsened by voluntary action and associated with overflow muscle
activation.

Motor Phenomenology Relevant To Dystonia

• Voluntary action: influenced by voluntary movement or voluntarily maintained posture.

• Dystonic tremor: oscillatory, rhythmical, inconstant, patterned movement produced by dystonia

often exacerbated by an attempt to maintain primary posture ± “null point”.
• Overflow: unintentional muscle contraction which accompanies primary dystonic movement.

• Mirror dystonia.
• Alleviating maneuvers (sensory tricks or gestes antagonistes).

• Task-specificity: selective activation of involuntary movements by specific tasks (e.g. writing,

playing music).

Symptomatic (secondary) dystonia.

1. CNS tumour, congenital malformation, or stroke, trauma.

2. Perinatal cerebral injury (cerebral palsy).

3. Viral encephalitis, subacute sclerosing panencephalitis, prion disease, tuberculosis
4. Vasculitis: SLE, Sjögren's syndrome.
5. Drug induced: levodopa, dopamine antagonists (e.g., neuroleptics, prochlorperazine,
metoclopramide), SSRI, buspirone, cocaine, monoamine oxidase inhibitors, flecainide, calcium
antagonists.
6. Toxins, e.g., CO, managanese, cyanide, methanol, disulfiram, carbondisulphide, and methanol.
7. Metabolic: hypoparathyroidism

8. Paraneoplastic syndromes

Evaluation of Dystonia
1. Lab: clinical, ceruloplasmin, s copper, 24 hr copper in urine, AFP, Cholestrol, ferritin,…organic
amine acids,..

2. MRI brain: NBIA, Wilson’s disease, secondary dystonia, HD, CBD.

3. Response to treatment.
4. Genetic testing on a research basis.
5. Others,…slit lamp examination, fibroblast cholesterol esterification

Wilson's Disease (WD)

 • Wilson's disease (WD) is a rare inherited multisystemic disorder of chronic copper toxicity,
resulting from the inability of the liver to excrete excessive dietary copper into bile.

• The disease manifests in children and young adults with liver, brain, or osseomuscular
impairment.
• Studies from various parts of the world suggest that diagnosis of WD is often delayed by several
years.

• Prevalence at least of approximately 1 case in 30,000 live births in most populations.

DIAGNOSIS
• ↑24-hour urine copper excretion

• Serum copper
• ↓↓Serum ceruloplasmin
• Liver functions,....

• Kayser-Fleischer rings – slit-lamp exam

• Liver biopsy; hepatic copper concentration - > 250 µg/g dry weight.
• MRI brain

Treatment of WD
Goal of Treatment
• to chelate excessive copper that has accumulated over the years as well as prevent ongoing
copper deposition.

• Symptomatic patient  restore normalcy (reverse neurological disability + stabilize liver

disease) + ensure continued normalcy

• Presymptomatic patient prevent symptom onset

• First-degree family members  rule out WD by mutational analysis or follow family members
well Into adulthood (preferably biannually) for clinical or laboratory evidence of WD.
 Headache

Classification of Headache
Primary Headache (No underlying cause) (The vast majority of headaches that primary care
physicians encounter are primary headaches)

 Migraine
 Tension type headache
 Cluster headache and other trigeminal autonomic cephalalgias

Secondary Headache (Underlying cause)

 Vascular cause (as subarachnoid hemorrhage or sinus thrombosis)
 Traumatic (head/neck injury)

 Space occupying lesion (as brain tumor)

 Infectious cause (as meningoencephalitis)
 Idiopathic increased intracranial tension
 Extracranial (sinusitis, glaucoma, TMJ disorders)
 Medication overuse headache

Primary or Secondary headache

Primary headache
• No other causative disorder

Secondary headache
• Usually newly experienced headache

• Usually associated with another disorder that is a known cause of headache (either intracranial
causes or systemic causes)

Red flags for headache (Always suspect secondary headache)

 Older patient groups (headache above age of 50)
 New-onset headache
 Sudden, worst headache of one’s life
 Progressive headache
 History of head trauma
  Altered level of consciousness
 Presence of systemic symptoms (fever, weight loss)
 Presence of abnormal neurologic signs (Do not miss examination of a patient)

Characteristics of migraine headache

 Unilateral or bilateral location
 Shifting of side in various attacks
 Pulsating quality
 Moderate or severe intensity (inhibit or prohibit daily activities)
 Aggravated by walking stairs or similar routine physical activities
 Associated with nausea, photophobia, phonophobia, dizziness

 Aggravated by hunger, sleep abnormalities, physical exertion, menstruation

 May be preceded by Aura consisting in the form of:
1. fully reversible visual symptoms including positive features (eg, flickering lights, spots or lines)
and/or negative features (ie, loss of vision)

2. fully reversible sensory symptoms including positive features (ie, pins and needles) and/or negative
features (ie, numbness)

Treatment of migraine
 Acute or Abortive treatment (Paracetamol, NSAIDs, Ergots, Triptans)

 Preventive treatment is needed if frequent attacks, long-lasting headache, disabling attacks or

overuse of abortive treatments
 Propanolol
 Topiramate

 Valproate
 Amitriptyline
 CGRP antagonists

Tension type headache

• Bilateral, pressing/tightening (non-throbbing) headache of mild or moderate intensity that
extends from forehead to side of temples and involves neck muscles
• Examination may show tenderness of pericranial muscles
 • Most of the patients treat with OTCs do not seek medical advice

Trigeminal autonomic cephalalgias.

• Headache
– Orbital
– Supraorbital
– Temporal

• Parasympathetic stimulation
– Lacrimation
– Conjunctival injection
– Nasal congestion

• Sympathetic signs
– Horner’s syndrome

Cluster headache
 Common in males around 30-50 years of age
 Severe or very severe unilateral orbital, supraorbital and/or temporal pain lasting 15-180 minutes
if untreated
 Headache can awaken the patient from sleep
 Headache is accompanied by at least one of the following:
1. Ipsilateral conjunctival injection and/or lacrimation
2. Ipsilateral nasal congestion and/or rhinorrhea
3. Ipsilateral eyelid edema

4. Ipsilateral forehead and facial sweating

5. Ipsilateral miosis or ptosis
6. A sense of restlessness or agitation

Headache due to idiopathic increased intracranial tension

 Usually diffuse, constant, daily occurring headache that is aggravated by cough and straining
 Clinical examination reveals papilledema
  Intracranial diseases especially sinus thrombosis ruled out by appropriate investigations (MRI
brain and MR venography)

 Lumbar puncture shows evidence of increased intracranial pressure(˃20 cm water)

 Headache improves after withdrawal of CSF to reduce pressure

Approach to Headache
• Careful history and examination; testing of motor and sensory function, cranial nerves,
reflexes, coordination and gait assessment and mental status evaluation, fundus examination.

• Consider secondary headache and proceed to diagnostic tests if any red flag or in patients
who were diagnosed as primary headache then began to develop new-onset atypical features or
treatment failure.

• As a rule, when assessing patients with headache, it is important to consider both the most
common etiologies of headache, as well as the life-threatening etiologies of headache.

Diagnostic testing
 CT brain is often the initial imaging test of choice for evaluating possibly emergent causes of a
headache.
 The use of CT brain should be considered in patients who present with “Red Flag” symptoms,
have new onset headache or changes in the nature of their headache.
 Patients with suspected subarachnoid hemorrhage or intraparenchymal hemorrhage should be
evaluated with CT head for evidence of bleeding (which will show up brightly on a CT of the
head if acute blood).
 CNS INFECTIONS
Importance
• Acute infections of the intracranial central nervous system (CNS) often present as neuro-logical
emergencies, where missed or delayed diagnosis and treatment can be catastrophicto the patient.

• Accurate and timely identification of the underlying etiologies, which are critical in directing
life-saving therapies, is mandatory .

Important Definitions
• Meningitis : inflammation of the meninges
• Encephalitis : inflammation of the brain parenchyma

• Myelitis : inflammation of the spinal cord

Meningitis
Pathogenesis of bacterial meningitis
• Nasal Mucosa

• Bacteremia
• CNS infasion ( Dural venous sinus, cribriform plate or choroid plexus

Pathogenesis of viral meningitis

• Spread across the blood brain barrier by replication in the capillary endothelial cells of the
cerebral blood vessels or choroid plexus .
• Carried across the barrier by infected leukocytes , the so called Trojan horse mechanism .
• Other routes includes spread via the olfactory nerves
• Centripetal spread via peripheral nerves , ( poliovirus )

Clinical Picture
• Most Patients ( Immunocompetent patients ) presented with Two of the following :

• Headache
• Fever
• Neck Stiffness

• Altered mental status

• Other signs of meningeal irritation or minigism includes positive kernigs and brudzinski sign
 • The kernigs sign is positive if when the patient is supine with the hip and knee flexed at 90
degree, forced extension of the knee cause pain in the lower back and or posterior thigh .
• The brudziski is positive if forced flexion of the neck causes knee and hip flexion .
• These signs have low sensitivity but high specificity for meningitis

• The sensitivity is particularly poor for patients with only mild CSF pleocytosis , for example the
severely immunocompromised and those with fungal or viral meningitis

Important Items in history

• Recent travel to meningitis belt in Africa, or haj in Saudi Arabia ,
• Leptospirosis from a rat urine during fresh water activities
• Ongoing disease epidemic

• Risk factors for HIV should be assessed properly as intravenous drug users ,

• If meningitis is associated with genital ulcers herpes simplex virus 2 , may be the cause ,
specially if recurrent meningitis

• It is important to ask if the patient is at risk of infection because of immunocompromised, recent

head injury , or neurosurgery

• Length of the history is important most of common viruses and bacteria cause acute presentation,
in contrast tuberculosis , fungi , parasites and non infectious causes such as carcinoma are most
likely to present chronically

Examination
A thorough general medical examination is essential with suspected meningitis
• Purpuric meningococcal rash , Measles rash .
• Lymphadenopathy and tonsillitis are consistent with infectious mononucleosis
• Parotid swelling and orchitic suggest mumps meningitis

• Antecubital fossa, and groin inspection for possible intravenous drug injection sites which may
suggest an unusual organism
• Oral candidiasis or hairy leukoplakia inside the mouth which is found in immunocompromised
HIV patients .

• Lymphadenopathy is suggestive of tuberculosis or HIV

• If there is history of head trauma , look carefully for CSF leakage , from the nose or ears
suggestive of a skull base fracture
• Examine ear for infection which is a risk factor for pneumococcal meningitis .
 • Pneumonia is a risk factor

Important Points in neurological examination :

• document coma score
• flexors and extensors response to pain

• Examine for papilledema and focal neurological signs particularly those suggestive of brain
herniation

• Multiple cranial neuropathies are characteristic for of some basal meningitis process including
tuberculous meningitis , carcinomatous meningitis , enterovirus meningitis , and sarcoid
• Funduscopic examination may reveal changes of tuberculoma , or cytomegalovirus retinitis

Investigations
• Laboratory Investigations ( CBC, Kidney and Liver functions tests )
• Brain Imaging
• CSF analysis

CSF Findings in central nervous system infections

• A plasma glucose should be taken immediately before lumbar puncture , so that the CSF plasma
glucose ratio , can be determined

• Gram staining of the CSF permits rapid identification of the causative organism in acute bacterial
meningitis

Complications of acute bacterial meningitis

• Subdural empyema
• Venous thrombosis and thrombophlebitis
• Subdural effusion
• Cerebral or cerebellar herniation
• Septic Shock
• Aspiration pneumonia

• Hyponatraemia

Specific Causes of meningitis

Pneumococcal meningitis
 • Streptococcus Pneumonia or Pneumococci are small 0.8 micron, non spore forming , non motile
gram positive cocci that typically appear in clinical specimens as a lancet shaped pairs,
diplococci, with tapered ends in juxtaposition.
• On blood agar culture plates, they are alpha hemolytic

• As with other major bacterial meningeal pathogens , pneumococcal meningitis often follows
recent nasopharyngeal colonization by a virulent strain.

• Asymptomatic carriage of virulent strain of pneumococcus is common , occurring for 5-75

percent of normal adults

Risk Factors
• Foci of Pneumococcal infection elsewhere
• Acute otitis media
• Acute sinusitis

• HIV
• Childhood nephretic syndrome

• Asplenia
• Chronic lymphocytic leukemia

Clinical Picture
• More severe than other forms .
• 11-19 % are comatosed on admission
• 7-21 % have seizures

• 29-42% have focal neurological deficit ( Weisfelt et al., 2006 )

Diagnosis
• Gram stain positive in 81-93 % of patients

• CSF culture is positive for 76-88 percent

• Imaging of patients with pneumococcal meningitis shows hypodense lesions suspicious of

infarction in 17-30 %.
• brain swelling in 20-39 % and hydrocephalus in 5-16 % .
• Cortical vein or venous sinus thrombosis may also occur

Treatment & vaccination

 • Third generation cephalosporin plus vancomycin

• There are two vaccines used against pneumococcal disease , targeting the cell wall
polysaccharide antigen .

Meningococcal meningitis
• Niesseria meningitides is a non spore forming , non motile gram negative diplococcus, that
usually appears kidney shaped in clinical specimen . Based on the antigenic characteristics of the
capsular polysaccharide, 13 serogroups are recognized, of which A, B, C,Y ,W-135 are the most
important . Serogroup A is prevalent in Africa, whereas B, C, and Y are more important in
Europe and America.

Risk factors
• Living in college or dormitories , household crowding , low socioeconomic status , active and
passive cigarette smoking
• Travel to countries with endemic or hyper endemic disease

• Antecedent viral infection especially influenza A may predispose to invasive pneumococcal

disease .

• Other risk factors include impaired complement system , complement depletion due to nephrotic
syndrome , hepatic failure, myeloma , systemic lupus erythematosus, asplenic state , HIV , and
hepatitis C

Clinical Feature
• Meningococcus commonly cause two clinical syndromes, which may overlap: septicemia and
meningitis .
• Menigiococcal septicemia present with fever , chills, malaise , prostration , and a rash .

• A non petechial purpuric rash is the classical finding , but urticarial and maculopapular rashes
may also occur .
• Shock with disseminated intravascular coagulation .

• The waterhammer friderichsen syndrome , can rapidly follow the development of

meningococcemia , leading to coma and death .

Diagnosis , treatment , and outcome

• The diagnosis is conformed by the presence of gram negative diplococci in the CSF, or cultures
from CSF , blood , or skin lesion

• Early treatment with empirical antibiotics is helpful , penicillin G , and ampicillin have been the
antimicrobial agents of choice for N. meningitides, though reduced susceptibility to penicillin is
being reported with increasing frequency .
 • Third generation cephalosporin are often used as first line treatment .

Tuberculosis meningitis
Risk factors include
• HIV
• Increasing multidrug resistance
• Increasing travel

Microbiology and Pathology

• Mycobacterium tuberculosis is an obligate aerobic bacterium whose only natural reservoir is
humans, humans become infected following inhalation of infectious particles . There is
replication within macrophages in the alveoli for two to four weeks , during which there is no
immune response .

• During this period haematogenous spread through the body occurs , the subsequent course
depends on the host response . There may be compete elimination by macrophages , leaving no
residua, of infection except for a positive tuberculin test .
• Alternatively casieous foci surrounded by fibrous capsules , tubercles may develop .

• Viable mycobacteria are controlled within tubercles, but not eliminated , thus they are ready to
reactivate if the host’s immunity wanes in the future .

Clinical Clues
• Basal meningitis and adhesions lead to multible cranial nerve affection
• Military tuberculosis
• Optic atrophy
• Involuntary movements
• Symptoms more than 6 days

• Chest Radiographs show active or previous tuberculosis

Diagnosis
• C. S.F criteria

• Direct microscopy of CSF of acid fast by Zeil Nelsen stain , culture is more likely to be positive
with large volumes .
• PCR for TB is sensitive in 50 % of patients , and specific for 95 % of patients

Treatment
 • Rifampicin, isoniazide , pyrazinamide , and ethambutol. (two months).
• For the continuation phase rifampicin and isoniazide are recommended .

Fungal Meningitis.
• Risk Factors :
• HIV
• Transpalnts
• corticosteroids

• chemotherapy

Pathogenesis and route of infection

• Most Pathogenic fungi are dimorphic as a unicellular yeast , or filamentous hyphae, that grow by
extension and produce spores , which subsequently cause fungaemia , and then invade the
meninges or brain parenchyma .

• Zygomycetes invasion occurs secondary to chronic sinusitis , other less common routes include
indwelling catheters, and skin wounds .
Fungi can be divided into :

• Those which can cause disease in both healthy an immunocompromised individuals :

Cryptococcus neoformans , Histoplasma capsulatum, Blastomyces dermaditidis , coccidiodes sp

• Those which are only seen in susceptible individuals with immunocompromised or anatomical
abnormalities : candida species, Aspergillus species and zygomaticus species , which is also
known as mucormycosis

Clinical Suspicion
• Subacute course
• Basal Meningitis and multiple cranial nerve affection
• Raised intracranial pressure and papilledema

• Abscess formation
• Zygomycetes also known as mucomycosis begins as a nasal or sinus infection, with black nasal discharge,
facial pain , cellulitis.

• The fungus erodes into the cranium , causing a cavernous sinus thrombosis, with cranial neuropathies

Diagnosis
• Elevated opening pressure
 • Moderate lymphocytic pleocytosis of 20 to 1000 cells/mm ( )
• Low glucose

• Elevated proteins
• Indian ink staining is positive in 80% of cases of Cryptococcus.

• Cryptococcal antigen testing is positive in most patients .

• Identification and isolation rates for other fungi in the CSF are much less.

Treatment
• Amphotrecin B is a polyene

• Flucytosine : nucleoside analogue

• Fluconazole and other azoles

ENCEPHALITIS
• Inflammatory changes affecting brain parenchyma.
• Viruses are the most common infectious causes

Viral causes of acute encephalitis

• Directly transmitted :

• HSV type 1 : the most commonly diagnosed sporadic encephalitis

• HSV type 2 : meningitis , meningoencephalitis occur in immunocompromised or neonates
• Varicella Zoster virus type 1 : cerebellitis
• EBV : encephalitis in immunocompromised

• CMV : Encephalitis in immunocompromised with retinitis , radiculitis , neutrophilic CSF with

low glucose

• Human Herpes Virus 6& 7 : febrile convulsions in children , encephalitis in

immunocompromised adults

Pathogenesis of viral encephalitis

• The virus enter the body via mucosal surfaces of the respiratory , oral , gastrointestinal tract ,
occasionally through the cornea ;

• Because they have been inoculated across the epidermis of the skin by a biting insect, by bite or
scratch of an animal or via a needle.
• Means by which viruses enter the CNS ;
 • 1- Viraemia with spread across the vascular endothelium. This applies to enteroviruses , such as
poliovirus, arbovirus such as west Nile virus. The virus initially replicates locally in the skin , or
mucosal surface and possibly by local lymph tissue. This leads to a primary viraemia, during
which more distant tissue of the reticuloendothelial system is infected , including the liver and
spleen. Replication in these tissues leads to secondary viraemia. And then spread into target
organs including the central nervous system, This occurs by replication in the vascular
endothelium of the choroid plexus , of the meniges , and of the brain itself; alternatively the virus
may be passively transferred across the endothelium.

• Centripetal spread along nerves, this is thought to apply to herpes simplex virus following initial
infection of the nasopharyngeal of genital mucosa, and to rabies virus following a bite or scratch
from an infected dog or bat . Rabies virions continuo to replicate , and spread centrifugally down
axons, so that virions are secreted in saliva and other body fluids.
• Carriage within immune cells that cross the blood brain barrier . This is demonstrated by HIV
which enters the Central nervous system ( Trojan horse like within leucocytes that are crossing
the blood brain barrier . HIV enters T lymphocytes using the cell surface protein CD4

Clinical approach to patient with encephalitis

Fever
Altered consciousness

Headache
Seizures
Alternative explanation for coma or level of consciousness
Intravenous drug abuse
Urinary infection

Investigations
• Peripheral blood count ( leukocytosis, leucopenia, atypical lymphocytes in EBV infection )
• Chest x ray ( pulmonary infiltrates )
• Lumbar Puncture

• MRI BRAIN

Diagnostic Virology
• CSF Polymerase chain reaction ( PCR)
• HSV 1, HSV 2, VZV, Enterovirus

• EBV, CMV ( Immunocompromised )

 • Special circumstances ( rabies , west Nile virus , tick borne encephalitis virus
• Antibody testing
• IgM, IgG in CSF and serum ( HSV, Varicella Zoster virus , CMV )
• Ancillary Investigations : Throat swab , nasopharyngeal aspirate , rectal swab , PCR for
nasopharyngeal aspirate for respiratory viruses , adenoviruses
• Imaging : Brain MRI shows high signal intensity in the affected brain areas
• EEG shows non specific diffuse high amplitude slow waves of encephalopathy .
• Periodic lateralized discharge

Acute management
• Antiviral therapy
• Control immediate complications of encephalitis

• Prevent some of the late complications

Antiviral and immunomodulatory therapy

• Acyclovir : 10 mg/kg every 8 hours for 14-21 days
• Steroids and mannitol if associated brain swelling and oedema

• Gancyclovir
• Management of seizures and raised intracranial pressure

Encephalitis ( Specific Pathogens)

• Herpes Simplex virus
Most common viral infection in western industrialized nations .
Ninety percent of cases due to herpes simplex type 1 , and 10% due to herpes simplex type 2

Pathogenesis
• More than two third of cases of herpes virus are thought to be activated by latent virus .

• Primary infection with herpes simplex virus type I occurs via the oral mucosa where it may give
ulcers or be asymptomatic.

• Following the primary infection the virus travel along the trigeminal nerve to cause latent
infection of the trigeminal ganglion .

• Pathologically the damage principally affect the limbic system , and nearby structures , thus the
temporal lobes are most often affected, along with the inferior frontal lobes .
Clinical Features
• Acute flu like prodromal

• Then into an illness with high fever , headache , nausea , vomiting and altered consciousness
• Seizures and focal neurological signs

• Alterations in higher mental function include lethargy, drowsiness, confusion , disorientation

and coma .

Herpes Simplex type II encephalitis

• Transmitted via the genital mucosa causing genital herpes in adults .

• It cause meningitis and encephalitis specially in neonates

Neonatal encephalitis
• Neonatal herpes simplex virus 2 infection occur in utero , intrapartum, or postnatally .

• Acquisition during delivery

• Seizures , generalized or focal , lethargy , irritability , tremors , poor feeding , temperature

instability and bulging fontanelle .
• CSF pleocytosis , PCR , High protiens

Varicella Zoster virus infection

• Encephalitis

• Vasculopathies affecting large or small vessels disease , or neuropathies such as Ramsy Hunt
Syndrome .
• The neurological complications can be divided into those associated with primary infection, and
those associated with reactivation .

• Primary infection with varicella zoster virus cause chicken pox , following this the virus become
latent in neurons from which it may emerge decades later to cause shingles, or zoster

• Infection occur through droplet infection from children with chicken pox, or virus shed at the
time of shingles .

Brain Abscess
• Focal intracerebral infection , initially as a localized area of cerebritis , develop into a collection
of pus surrounded by a well vascularized capsule .

Pathogenesis
 • First Stage of formation is of early cerebritis , with perivascular inflammatory changes and
edema surrounding the area of brain necrosis.

• Then progression to necrosis of the center , fibroblasts and neovascularity appear at the periphery
and begin to form a capsule .
• Astrocytic reaction is induced and white matter oedema spread

• Early capsule formation continues with the development of further fibroblasts, peripheral
vascularity , oedema and reactive astrocytosis .

The presentation of brain abscess depends on :

• location

• Virulence of the organism

• Host defences
• Age of the patient

• The severity of the primary infection

Investigations
• Brain Imaging : showed a contrast enhancing ring surrounded by oedema

Subdural Empyema
• Accumulation of pus in the potential space between the dura mater and arachnoid mater .
• It is more likely to collect over the convexities of the cerebral hemisphere

• Parafalcine region

• Tentorium cerrebilli because brain is not closely applied to the dura in this area as it is in the
region of the venous sinuses .

Clinical Feature
• Signs of infection ( pyrexia , palpitation , tachycardia , rigors ) evidence of local infection
• Signs of raised intracranial tension

• Focal signs of hemiparesis , dysphasia , nystagmus

• Siezures

Investigations
• Complete blood count
• ESR
 • C reactive protein
• Brain imaging ( CT or MRI )

Management
• Antibiotics
• Management of increased intracranial tension

• Management of seizures
• Surgical ( aspiration )