NEUROLOGY REVIEWThe bare bones of the thing

Cerebrovascular Disease

Neurodegenerative Conditions

Epilepsy

Demyelinating Disease

Neuropathies

Headaches

Neuromuscular Conditions

Cerebrovascular Disease

• Risk factors: Age, Family Hx, HTN, Cholesterol, Diabetes, Heart Disease (esp Afib, cardiomyopathy, atrial thrombus, PFO), tobacco use, excessive etoh use, hypercoagulable states (cardiolipin syndrome, CA, anti-thrombin 3 deficiency, prot C and prot S deficiency)

Ischemic vs Hemorrhagic

• Ischemic strokes of sudden onset or stuttering in onset

• Deficits worse at onset with gradual improvement

• Most common type(85%)

• Hemorrhagic strokes of sudden onset

• Deficits worsen with time

• Headache is common

• Additional etiologies: AVM, aneurysm, amyloid angiopathy

Thrombotic vs Embolic

• Clinically, impossible to differentiate• Most strokes are thrombotic (?80%)• If potential source is identified (Carotid

stenosis, Afib, atrial thrombis, cardiomyopathy, endocarditis, PFO, aortic arch plaque, dissection) then assume embolism. Otherwise, assume intracranial thrombosis.

Left Hemisphere

• Right hemiparesis, hemisensory deficit

• Aphasia if cortical location

• Hyper-reflexia on right, Babinski on right

• Initially flaccid tone with eventual spasticity on right

Right Hemisphere

• Often silent or less pronounced symptoms due to the dominance of the left hemisphere

• Left hemiparesis, hemisensory deficit• Anosognosia• Hyper-reflexia on left with left Babinski• Initially flaccid with eventual spasticity

on left

Occipital infarcts

• Left or right hemi-visual field loss• Headache common• Patient often misinterprets that one eye doesn’t work. The

examiner needs to discern the truth by checking visual fields

Cerebellar infarcts

• Objectively: Ataxia, dysdiadachokinesis, tremor, dysarthria, nystagmus

• Subjectively: Dizziness, nausea, clumsiness

• Higher risk of hemorrhagic transformation compared to other brain areas

Brainstem Infarcts

• Cranial nerve signs: diplopia, facial numbness, facial weakness, ptosis, pupil irregularities, dysphagia, asymmetric palate or tongue,

• Crossed motor or sensory deficits, or even biparesis or quadraparesis

Transient Ischemic Attacks

• Three minutes or less. This is a meaningless distinction. The event is still a stroke.

• Most significant is Amaurosis Fugax. “Fleeting Blindness” may represent embolic event from carotid stenosis

• Any TIA is a harbinger of another stroke in the near future (15% chance within a month)

Workup

• MRI brain is preferable. CT’s are quick• Carotid Duplex. MRA or CT angiogram

if dissection is suspected• TTE or TEE• EKG/Holter• Hypercoagulation blood work if

indicated

Emergent Treatment

• Anti-platelet medication at onset (except, of course, in hemorrhage)

• Anti-coagulation if embolism from Afib, atrial thrombus, or cardiomyopathy, or dissection is determined

• tPA if available within three hours of onset.

Prevention

• Anti-platelet medication in almost all cases• Anti-coagulation only in Afib, cardiomyopathy,

atrial thrombus, “shaggy aorta syndrome”• Carotid endarterectomy if ipsilateral stenosis

greater than 70%• PFO closure• Treatment of underlying risk factors

Neurodegenerative Conditions

• Alzheimer’s Disease

• Parkinson’s Disease

• Huntington’s Disease

• Progressive Supranuclear Palsy

• Cerebellar Degeneration

Alzheimer’s Disease

• Estimated 50% of people age 85 years

• Familial if parent had disease in early to mid 50’s

• Risk factors: loose association to past head injuries, inverse association to IQ and education level

AD Pathology

• Neurofibrilary tangles, neuritic plaques

• Generalized brain atrophy as disease progresses, but especially in temporal lobes

• Reduction in acetylcholine system

AD symptoms/signs

• Progressive “short term” memory deficits, i.e. inability to form new memories.

• Progressive aphasia

• Personality change

• Progressive deficits in ADL’s - Apraxia

AD Workup

• Brain imaging

• B12 level, TSH

• Mini Mental Status exam

• Clock Drawing

AD continued

• The leading cause of dementia in the USA is Alzheimers.

• The second leading cause is multiple strokes

• The third cause is a combination of the two above.

AD Treatment

• Acetylcholine esterase inhibitors - Aricept, Exelon, Razadyne

• Glutamate inhibitor - Namenda• These drugs only slow the progression

of the disease, they do not lessen the deficits

• In this disease, you treat the family perhaps more than the patient

Parkinson’s Disease

• Very common - estimated one in one hundred between ages 60 and 70 years

• Tends to be sporadic

• Rate of disease progression is very variable

PD Pathology

• Progressive degeneration of pigmented dopamine producing cells in the substantia nigra, i.e. nuclei in the mid-brain

• Degeneration begins at birth.

• Symptoms appear when degeneration reaches 80%

PD Symptoms/Signs

• Tremor - Resting. Often begins unilaterally in extremities. Can involve the jaw and tongue

• Rigidity - increased tone in the extremity muscles. Cogwheeling if superimposed tremor. Stooped posture

• Akinesia (bradykinesia)• Postural Instability

PD Symptom/Signs continued

• Drooling, constipation, micrographia, low volume stuttering speech, dementia, reduced facial expression, reduced eyeblink rate

PD Treatment

• Neuroprotective agents: Vitamin E, CoEnzyme Q10• Dopamine agonists: Requip, Mirapex, Permax. More

useful early on when there are more dopaminergic cells still functioning

• Anti-cholinergics especially for tremor• Dopamine replacement: Sinemet

(carbidopa/levadopa). Gold standard treatment (high risk of adverse effects at five years) - Less is Best

• Deep Brain Stimulation

Huntington’s Disease

• Autosomal Dominant disorder. • Easily diagnosed via blood test that detects the

genetic defect, i.e. CAG repeat sequence - the longer the sequence, the earlier onset and more severe the symptoms

• Symptoms usually manifest in young adulthood

HD Clinical triad

• Chorea - involuntary, writhing or quick movments of face, limbs, trunk

• Psychiatric disease - usually depression and can occur before other deficits

• Dementia - usually occurs later

HD Treatment

• Is a progressive disease. Life expectancy average 19 years

• No known treatment, except to treat the depression when needed or to reduce the chorea with dopamine blockers. Dementia is resistant to treatment

• Again, treat the family

Progressive Supranuclear Palsy

• Usual onset 6th to 7th decade• Sporadic• Pathology - degeneration of brain stem

nuclei in midbrain “and above” to the basal ganglia

• Often mistaken for Parkinson’s Disease because of the bradykinetic appearance of the patient

PSP Continued

• Hallmark Sign: impaired voluntary vertical eye movements

• Also, axial more than appendicular rigidity, grimacing, drooling, dysarthria

• Prominent early symptom: Falling especially going down steps (due to impaired vertical eye movements)

PSP continued

• Treatment - none

• This is another disease where the treatment is directed more to the family than the patient

Cerebellar Degeneration

• Autosomal recessive types tend to occur early adulthood

• Autosomal dominant types tend to occur later life

• Both are slowly progressive and similar in deficits

CD continued

• Progressive ataxia, dysarthria, irregular tremor in extremities and trunk (titubation), dysphagia, nystagmus

• Dementia is subtle and generally not significant

Epilepsy

• A seizure is a single event due to an abnormal discharge of a group of cerebral neurons resulting in a multifarious array of behaviors and/or cognitive experiences

• There are many etiologies for seizures - trauma, hypoxia, drugs, fever, etc.

Epilepsy Continued

• Epilepsy is a disorder of the brain that produces recurrent spontaneous, seizures.

• Two age peaks - childhood to young adult and later life (age 55+)

• Younger group has 5-20%chance of resolution and is often hereditary. Older group has little to no chance of resolution and is usually sporadic.

Types of seizures

• Simple Partial - motor, sensory, visual, cognitive or emotive event (depending on location of the electrical discharge) WITHOUT change in consciousness

• Complex Partial - the above WITH change in consciousness

• Generalized Tonic-Clonic Seizure• Absence, Myoclonic, Atonic, Tonic, Clonic

seizures

Types of Epilepsy

• Partial Epilepsies (location specific) result in simple partial, complex partial or secondarily generalized tonic-clonic convulsions. An abnormal electrical focus in the brain may be due to scar, tumor, congenital malformation

• Primary Generalized Epilepsies result in absense, myoclonic, tonic, clonic seizures or tonic-clonic convulsions. No abnl focus is found. Rather, the brain has lower seizure threshold.

Epilepsy workup

• Obtain as complete a history as possible

• EEG to determine type of Epilepsy (recall EEG’s only 90+% sensitive)

• Brain imaging re possibility of mass, stroke, etc.

• Select urine tox screen or blood studies as indicated

Epilepsy Treatment

• Medication choice depends, in part, on type of Epilepsy

• Primary Generalized Epilepsies respond best to Depakote, Lamictal, Keppra and Topamax. Avoid Tegretol.

• The Partial Epilepsies respond to all medications

Epilepsy treatment continued

• The Generalized Epilepsies are usually more successfully treated, whereas the Partial epilepsies are more challenging.

• 70% of people are 100% controlled on monotherapy. The remainder require polypharmacy and may not have 100% control

• Vagus Nerve Stimulation and lesionectomy or corpus callosotomy are used in refractory cases.

Epilepsy medication side effects

• Depakote - spina bifida, weight gain, tremor, hair loss

• Tegretol - hyponatremia• Dilantin - gingivitis, hirsutism,

osteoporosis• Topamax - renal calculi• Phenobarbitol - sedation and cognitive

impairment

Epilepsy and pregnancy

• Overall risk to mom and baby is greater if mom is untreated.

• Birth defect rate general population 2%

• Birth defect rate untreated epileptics 4%

• Birth defect rate treated epileptics 6%

• Supplemental folate, monitor drug levels, mom considered “high risk”

Status Epilepticus

• Thirty minutes or more of continuous seizing or recurrent seizures without recovery between them.

• Is an emergency because of potential neuronal damage due to high metabolic activity and hypoxia.

• Rx: Benzo first followed by IV Fosphenytoin and possibly IV phenobarbitol

CNS Demyelinating Disease

• Multiple Sclerosis is an auto-immune disease affecting both the brain and spinal cord in which myelin is attacked by anti-bodies. This results in destruction of the myelin and if severe can lead to axonal destruction and ultimately neuronal death.

• “Sclerosis” refers to the calcified scarring seen in multiple areas of the brain and/or spinal cord at autopsy

Demyelinating Disease continued

• If only the spinal cord is affected, the condition is referred to as Transverse Myelitis

• Once the brain is affected , the condition is referred to as Multiple Sclerosis

• It is a disease primarily of young women

MS - Course of the disease

• Relapsing-Remitting 70%

• Primary Progressive 10%

• Secondary Progressive - about 50% of the R-R type at 15 years

• Monosymptomatic - ?10%

• Devic’s Disease - TM plus ON only 5%

MS Workup

• MRI showing multiple (at least nine) peri-ventricular lesions typically perpendicular to ventricles, some of which enhance

• Lumbar Puncture revealing oligoclonal bands, myelin basic protein, elevated CSF/serum IgG ratio

• Visual Evoked Potential• Clinical criteria “dissemination in time and

space.” This is still the best way to diagnose

MS Symptoms/Signs

• Typical relapse is gradual onset (2d to 2w) of a neurologic deficit, plateau (2w to 2m) and gradual recovery

• Deficits include motor, sensory, balance, visual (Optic Neuritis in particular), speech, cognitive problems

• Fatigue, depression, dementia common and long lasting

• Average 2 relapses per year

MS Treatment

• Steroids useful in shortening the duration of a particular relapse and in reducing its’ severity

• Immunomodulating medications useful in reducing relapse rate, reducing “lesion load” in the CNS, and ultimately in reducing long term disability

MS Treatment continued

• Currently six options• Beta seron - LFT elevations, flu-like

symptoms, leukopenia• Avonex - as above but less problematic• Rebif - very similar to Beta seron• These three are all Interferons and suppress

B cell antibody production.Higher potency interferons are more efficacious but carry increased adverse effects.

MS Rx Continued

• Copaxone - subcutaneous necrosis. Acts by suppressing B cell antibody production and entrance to CNS

• Novantrone - cardiomyopathy and leukemia. Unclear mechanism of action

• Tysabri - Progressive Multifocal Leukoencephalopathy occurs in 1/3000 patients

• Two oral therapies just available.

NeuropathyDAMN THERAPISTS

• D Diabetes• A Atherosclerosis• M Monoclonal gammopathies• N Nutritional• T Trauma• H Hereditary• E Endocrine• R Rheumatoid Arthritis

Etiologies continued

• A Amyloid

• P Paraneoplastic syndromes

• I Infectious, idiopathic

• S Sarcoid

• T Therapy

• S Sjogren’s syndrome, SLE

Neuropathy continued

• Subjectively is a slowly progressive anesthesia/paresthesia/dysesthesia and/or weakness initially affecting the distal lower extremities that can eventually affect the upper extremities.

• Objectively it involves varying severity of sensory deficit and/or weakness with reduced or absent reflexes.

Neuropathy workup

• Nerve Conduction Velocity and Electro Myography (EMG) to help delineate type (axonal vs demyelinating) and severity

• Select blood work as related to Damn Therapists

• Rarely, nerve biopsy

Neuropathy - Guilliane-Barre Syndrome

• GBS is a sub-acute (2d to 2w) onset of sensory deficit and weakness initially in distal lowers progressing to uppers. It is often peri-infectious.

• Pathologically, it is thought to be an immune mediated attack on the sensory, motor and autonomic peripheral nerves and also the nerve roots.

• Technically, known as an acute, inflammatory demyelinating polyneuropathy

GBS continued

• This can result in cranial nerve deficits and life threatening cardiac arhythmias and diaphragmatic weakness

• Exam reveals sensory loss and weakness in extremities,reflex loss, often facial weakness, pupil irregularities and dyspnea.

• The patient has back pain due to nerve root inflammation

GBS continued

• Time is of the essence.• Plasmapheresis or IVIG is used to remove

the offending antibodies from the serum• Treatment shortens the duration and severity

of the attack and can save the life of your poor, innocent, woeful, unsuspecting patient.

• Unfortunately, there is a recurrent form of this disease (CIDP) which is progressive.

HeadacheWhat a PAIN!

• Migraine• Analgesic Overuse Syndrome (Rebound)• Cluster• Trigeminal Neuralgia• Temporal Arteritis• Pseudotumor Cerebri• CSF Leak (Low pressure) headache

Migraine

• Lifelong disorder, usually most prominent in reproductive years

• Females more than males• Usually hereditary• The imaging study is done to make sure

it is not a “secondary headache” (secondary to a brain tumor or ruptured aneurysm, or intracranial hemorrhage)

Migraine symptoms

• The pathophysiology involves activation of the Trigeminal-vascular system resulting in a decrease in serotonin, increase in substance P and other neuropeptides. This then results in either intracranial vasoconstriction, extracranial vasodilation or both

Migraine continued• Clinically, the manifestations fall on a wide

spectrum from mild HA to severe throbbing pain with N/V, photo, phono and osmophobia, lasting hours to days at a time and often accompanied by the most sincere wish to die, NOW! rather than endure another moment of torture.

• 85% of migraineurs experience only the extracranial vasodilation

• 15% experience also the intracranial vasoconstriction

Migraine Aura(This is the interesting part)

• The aura depends on which area of the brain is affected by the oligemia/hypoxemia.

• Occipital lobe - scintillating scotomas, visual field loss, metamorphopsia

• Temporal lobe - deja vue, jamais vue, altered emotions

• Parietal lobe - hemiparesis/hemisensory deficit• Frontal lobe - disinhibition, confusion• Global - stupor and coma

Migraine Rx

• Abortive - triptans act as serotonin agonists and lead to vasoconstriction (Imitrex, Maxalt, Zomig, Relpax, etc) thus reducing the pain

• Preventive - tricyclics act as serotonin agonists, some anti-convulsants act as glutamate inhibitors and some BP meds help prevent vasodilation

Analgesic Overuse SyndromeAKA Rebound

• Occurs when pt takes more than three days weekly of any combination of analgesics

• Typically, HA in the AM (when the analgesic has worn off). Pt then continually titrates the use of the medicine(s) throughout the day

• Drug potency increases over time (one Tylenol to three Motrin to Vicodin to Percocet to ER visits requiring morphine)

• Requires about 2-3 weeks to develop into Chronic Daily Headache

• Treatment - Stop the analgesics. Relief usually in 10 to 14 days.

Cluster Headache

• Typically middle aged males who smoke

• Unilateral retro-orbital pain with lacrimation, nasal congestion, Horner’s syndrome that builds up over 5-10 minutes and last 60-90 minutes.

• Clusters around the same time of day and/or season

Cluster Rx

• Abortive - Imitrex injection and prednisone taper

• Preventive - Verapamil, Lithium

Trigeminal Neuralgia• Severe, piercing, short duration pain in

one or several unilateral branches of the Trigeminal Nerve occurring multiple times daily often triggered by touch, chewing.

• Atypical TN – paresthesias rather than pain.

• MRI brain needed to rule out MS, brain stem tumor or ectopic vessel pressing on the Trigeminal Nerve

Trigeminal neuralgia Rx

• Most anti-convulsants help. Baclofen, a CNS muscle relaxant sometimes useful

• Surgical treatment in refractory cases, i.e. decompression if ectopic vessel is found, or permanent ablation of the nerve branch(s) or intracranial compression of the nerve

Pseudotumor Cerebri

• Idiopathic intracranial hypertension resulting in headaches, transient visual obscurations and tinnitus

• Exam reveals papilledema• Typically in females, obese or pregnant• Certain anti-biotics can induce it -

tetracycline, minocycline• Work up: MRI brain to rule out real tumor,

MRV to rule out venous sinus thrombosis and LP to document high opening pressure

Pseudotumor Rx

• Diamox used to reduce CSF production rate

• Sometimes repeat LP’s are required

• Optic Nerve Sheath Decompression in refractory cases

• Venous sinus stent if sinus clot is discovered

Low Pressure Headache

• Commonly occurs in a post LP situation, but CSF leaks can also occur both spontaneously and sometimes after trivial trauma.

• Initial W/U is LP (if thought to be spontaneous)• Additional work up is radionucleotide cisternogram

showing CSF leaks along spinal canal• MRI spine with gadolinium sometimes helpful• Rx Epidural blood patch sets up sterile inflammation

in dura, sealing the leaks.

Temporal Arteritis

• Nonspecific HA in anyone over 55 years.• Can be associated with jaw pain while chewing,

visual loss in one eye.• Pathologically, inflammation of temporal artery and

its’ branches (to masseter muscle or to optic nerve)• Work up is biopsy (Giant cells and vessel

inflammation) and ESR 55+• Treatment is long term steroids or

immunosuppressants

Neuromuscular Conditions

• Amyotrophic Lateral Sclerosis

• Myasthenia Gravis

ALS

• Progressive neurodegenerative condition confined to the motor system. Pyramidal cells of cortical motor strip to the anterior horn cells of spinal cord.

• Spares eye movements (?) but affects all other motor functions: facial control, tongue, swallowing, breathing, sphincter control, limb and trunk muscles

• 25% of patients alive at five years• Rilutek, a glutamate inhibitor, prolongs life about 13

months

Myasthenia Gravis

• Autoimmune disorder affecting old men and young women

• Blockade/destruction of post-synaptic acetylcholine receptors on muscles

• Hallmark is fluctuating weakness in certain muscle groups, typically brain stem (ptosis, diplopia, dysarthria) but can be generalized affecting breathing, limb and trunk muscles.

MG diagnostics

• Acetylcholine receptor antibody level. Sensitivity only 80%

• Repetitive Nerve Stimulation shows decremental response in the muscles.

• Exam reveals fluctuating signs in the office and increasing weakness with prolonged strength testing

MG continued

• CT chest to rule out thymoma (thought to be the source of the antibody production)

• Rx 1-Thymectomy if residual thymus or thymoma discovered 2-Mestinon (acetylcholine esterase inhibitor) as symptomatic treatment 3-immunsuppressants such as prednisone, Imuran or Cellcept

Summary

• Know your neuroanatomy• Listen to your patient• In an emergency “Don’t just do something.

Stand there.”• Learn to trust your instincts• Consult your colleagues when in doubt• Read. Read. Read.