CNS Disorders PDF

Jason Ryan, MD, MPH  Sudden alteration in behavior Due to transient brain pathology  Loss of consciousness Abnormal motor activity Abnormal sensation Range Mild: Loss of awareness (absence) Severe: Tonic-clonic  Many people have 1 seizure Often “provoked” Fe...

Jason Ryan, MD, MPH  Sudden alteration in behavior Due to transient brain pathology  Loss of consciousness Abnormal motor activity Abnormal sensation Range Mild: Loss of awareness (absence) Severe: Tonic-clonic  Many people have 1 seizure Often “provoked” Fever (children) Lack of sleep Drugs, alcohol Hypoglycemia Other causes more serious: tumors, strokes Multiple, unprovoked seizures is epilepsy Genetic: Juvenile myoclonic epilepsy Metabolic: Hyponatremia, hypernatremia, hypoMg, hypoCa Infection: Meningoencephalitis  Blood work EKG (cardiac syncope) EEG Brain imaging (CT or MRI) Sometimes lumbar puncture (LP) Electroencephalogram Records voltage changes in brain Different leads Frontal, parietal, occipital Characteristic patterns Image courtesy of Der Lange  Partial – One discrete part of brain Simple partial – No alteration consciousness Complex partial – Alteration consciousness Generalized – Entire brain effected Absence “Petit mal” Tonic-clonic “Grand mal” Atonic “Drop seizure” Myotonic Secondary generalized  Can occur with partial seizures Higher cortical areas affected Dysphasia Feelings of familiarity ("deja-vu") Distortions of time Fear Hallucinations  Epigastric "rising" sensation Common aura with medial temporal lobe epilepsy Sweating Piloerection Pupillary changes  Warning before major seizure Auras = simple, partial seizures Seizure affects enough brain to cause symptoms Not enough to interfere with consciousness Symptoms depend on area of brain Occipital lobe: flashing lights Motor cortex: muscle jerking (Jacksonian Seizure)  Transition period seizure  normal state Period of brain recovery Confusion, lack of alertness Focal neurologic deficits may present Variable time, minutes to hours  Most common site: temporal lobe Mesial temporal sclerosis Also called hippocampal sclerosis Neuronal loss in hippocampus Often bilateral but one side>other Can diagnose by MRI  Absence, myoclonic, and grand mal Common in children Absence seizures first (~5 years of age) Myoclonic seizures later (~15 years) Grand mal seizures soon after Hallmark: Myoclonic jerks on awakening from sleep Shock-like, irregular movements of both arms  Sudden impairment of consciousness No change in body/motor tone Last few seconds Usually remits by puberty Classic EEG finding: 2.5 - 5 Hertz spike wave activity superimposed on normal background EEG No post-ictal confusion Ethosuximide is first line treatment Blocks thalamic T-type Ca++ channels  Common: 2-4% children 30min Or seizure that recurs =27 (out of 30) is normal Oriented to time, place Repeat three objects, remember them Serial 7s or spell WORLD backwards Name an object pointed out (agnosia) Repeat a phrase Draw an object shown  Alzheimer’s disease - 60% of cases Multi-infarct dementia (stroke) ~20% of cases Lewy body dementia Rare stuff Pick’s disease NPH Creutzfeldt-Jakob HIV Vitamin deficiencies Wilson’s disease  Most common cause dementia Degeneration of cortex Contrast with basal ganglia in movement disorders Generalized  no focal deficits Characterized by loss of ACh cortical activity Deficiency of choline acetyltransferase Prominent in basal nucleus of Meynert and hippocampus  Amyloid Precursor Protein (APP) (on neurons) Apolipoprotein E (ApoE) - + Apolipoprotein E (ApoE) Epsilon 2 Allele Epsilon 4 Allele Beta Breakdown Product (cleavage) Alpha-Beta (AB) Amyloid CNS Buildup Alzheimer’s  Proteins in many diseases Extracellular deposits All stain with Congo red All have apple-green birefringence (polarized light) Disease process depends on where they are found Alzheimer’s: Brain  Major risk factor is age Disease of elderly Sporadic Early disease Down syndrome – APP on Chromosome 21 Familial Form: Presenilin 1 & 2 gene mutations  Other risk factors: African American race Family history Obesity Type II diabetes (insulin resistance) HTN, Hyperlipidemia Traumatic brain injury  Cortical atrophy Gyri narrow Sulci widen Hydrocephalus ex vacuo Ventricles appear larger due to atrophy  Beta Amyloid Plaques Neurofibrillary Tangles Hyperphosphorylated Tau protein in Neuron Image courtesy of Neurofractal Normal neuronal cell bodies with nuclei Neuronal cell body (with nucleus) Containing neurofibrillary tangle in Image courtesy of Patho Cytoplasm (dark purple stuff)  Patient may not notice cognitive decline Often brought in by family member Diagnosis: clinical Confirmed at autopsy  Memantine NMDA receptor blocker N-methyl-D-aspartate receptor (glutamate receptor) Side Fx: Dizziness, confusion, hallucinations Donepezil, galantamine, rivastigmine Inhibit acetylcholinesterase Side Fx: Nausea, dizziness, insomnia Vitamin E Believes to protect against oxidation  Second most common cause Dementia after multiple strokes Vascular risk factors: HTN, ↑chol, smoking Stepwise progression of symptoms Treat risk factors  Lewy body: protein alpha-synuclein Found in basal ganglia in Parkinson’s If found in cortex: LB dementia Triad Dementia Parkinson’s symptoms Hallucinations Image courtesy of Charles E. Driscoll, MD  Rare cause of dementia Affects frontal and temporal lobes Frontal: Change in personality, behavior Temporal: Aphasia Path: Pick bodies SPHERICAL tau proteins Not tangles like AD  “Spongiform encephalopathy” Intracellular vacuoles Caused by PrPSC prion Sporadic mutation Familial Transmitted Mad Cow Disease  PrPc (normal) PrPsc (abnormal) (abnormal) Beta-pleated Sheet  Rapidly progressive dementia Death within a year Classic features Ataxia “Startle myoclonus” Spike-wave complexes on EEG Diagnosis Brain biopsy (gold standard) Clinical criteria Jason Ryan, MD, MPH  Multiple Sclerosis Guillain-Barre syndrome Progressive multifocal leukoencephalopathy (PML) Postinfectious encephalomyelitis Charcot-Marie-Tooth disease Metachromatic leukodystrophy Krabbe's disease  Autoimmune demyelination CNS Brain and spinal cord White women in 20s & 30s is classic demographic Relapsing, remitting course (most commonly) Diverse neuro symptoms that come/go over time Fatigue is extremely common  Lymphocytes (T-cells) react to myelin antigens Myelin basic protein Interferon-gamma Recruit macrophages Type IV hypersensitivity reaction  Any neuro symptom possible Few classic ones important to know Optic neuritis Demyelination of optic nerve Pain and loss of vision MLF syndrome (INO) One eye cannot move medially on lateral gaze Bladder dysfunction Spastic bladder Overflow incontinence  MRI is gold standard Path: Periventricular plaques Oligodendrocyte loss Reactive gliosis CSF High protein Oligoclonal bands Images courtesy of DrKrupe  Rare patients do not require treatment 1 or 2 lesions, no flairs Interferon (avonex, rebif, betaseron) Newer agents: Natalizumab (Tysabri ) Dimethyl fumarate (Tecfidera)  Acute inflammatory demyelinating radiculopathy Schwann cells destroyed by immune system Ascending muscle weakness over daysweeks Starts in legs Spreads to other areas Respiratory failure 10-30% Facial muscle weakness >50% Sensory deficits occur (paresthesias) but mild Symptoms usually resolve over weeks to months  Autonomic dysfunction >70% Tachycardia Urinary retention Hypertension/hypotension Arrhythmias Ileus Loss of sweating Severe autonomic dysfunction can cause SCD  Often triggered by infection Classic agent: Campylobacter jejuni Bloody diarrhea Classic agent: CMV Usually asymptomatic infection Detected by rise in CMV antibodies Immunosuppressed patient (1-6months after xplant) Febrile illness  CSF shows elevated protein level Normal CSF cell count  Treatment: Respiratory support Plasmapheresis IV immune globulins Image courtesy of Mr Vacchi  Severe demyelinating disease of CNS Reactivation of a latent JC virus Demyelination: multiple white matter lesions imaging Destroys oligodendrocytes CD4 < 200 cells/mm3 Causes slow onset encephalopathy Altered mental status Focal neuro defects (motor, gait, etc) Dx: JC Virus DNA in CSF or brain biopsy  Acute onset multifocal neurologic symptoms Often rapid deterioration  hospitalization Rare sequelae of infection or vaccinations Mean 26 days after Infections: Varicella or measles Vaccines: Rabies, small pox Most common histopathology: perivenous infiltration Lymphocytes, neutrophils, other cells Inflammation/demyelination Images courtesy of Professor Yasser Metwally Hereditary motor and sensory neuropathy (HMSN) Progressive hereditary peripheral nerve disorders Onset usually late childhood/adolescence Defective production nerve proteins or myelin Leg muscles (bilateral) become wasted Legs have characteristic stork-like contour Footdrop Foot deformities usually develop Upper extremities also affected (