Neuro 3😊

MRI head:

• KF ring seen in eyes.
• Deposits in Descemet's membrane

• Giant face of Panda
• in midbrain on T2 MRI.

NOTE

• Panda sign is seen in sarcoidosis with Gallium-67 scan.

Treatment: 

• Copper chelators:
• Trientine (Triethylenetetramine)
• D- Penicillamine

• DOC (in maintenance phase):
• Zinc acetate

• DOC For neurological features:
• Tetrathiomolybdate

Neurodegeneration of brain due to Iron accumulation /
Halloverden Spatz disease

• Autosomal recessive neurodegeneration.

• Iron deposition in basal ganglia.
• Basal ganglia: Globus pallidus.

• MRI head: Eye of tiger.

• PKAN: Pantothenate kinase

• Hello Harsha verdan → Tiger eyes → Wear Pants

Imp

• Demyelination:
• Conduction velocity reduced
• Distal latencies

• Axonal:
• Low amplitude

Multiple Sclerosis:

• CNS demyelinating disease.

• Away from equator, Low Vit D → ↑ incidence

• There is plaque formation in the brain.

• Revised McDonald criteria
• Dissemination in time and space

• Charcots triad (SIN)
• SCANNING SPEECH
• INTENTION TREMOR
• NYSTAGMUS
• Due to MLF → Internuclear Ophthalmoplegia

• Lhermitte sign
• Shock like sensation down the spinal cord

• Uthoff sign
• Increases with temp

• Also called Dawson finger.

• U/L Optic nerve is involved.

• Presentation:
• Female patient.
• Mainly of Caucasian origin.
• Northern part of Europe origin.
• British women.
• One sided decreased visual acuity.
• Also has relative efferent pupillary defect.
• Optic neuritis.
• Bladder/bowel involvement.

• Autoimmune: 
• Antibodies against 
• Myelin basic protein 
• Oligodendrocyte glycoprotein.
• Oligodendrocytes attacked/killed by T-cells → Demyelination.

• Effect: 
• Decrement in nerve conduction velocity.

• Mnemonic:
• Myru nn pryunnath basic (Myelin basic protein) anu
• Olipich olipich (Oligodendrocytes) nadakkum

MRI head

Treatment:

• Acute episode/First presentation:
• Visual blurring, decreased colour vision:
• Methylprednisolone

• Mitoxantrone
• Most effective

Condition	DOC
Acute Episode	IV Steroids
Primary Progressive	Ocrelizumab
Relapsing Remitting	β-IFN

Prevention:

• β-Interferon

• Glatiramer

• Dimethyl Fumarate

• Monoclonal antibodies
• In worst case scenario
• Natalizumab
• S/E → Progressive Multifocal Leucoencephalopathy
• Aw JC virus
• Mnemonic: Nattelilu lesions varathirikan

PPMS (Primary Progressive Multiple Sclerosis):

• Ocrelizumab.

• Mnemonic: To progress → First Ocred (Ocrelizumab)

SPMS (Secondary Progressive Multiple Sclerosis):

• Siponimod.

• Mnemonic: Second sip

NOTE

• NMOSD (Neuromyelitis Optica Spectrum Disorder).
• Young female patient
• Sudden onset bilateral optic neuritis
• Recurrent

• In multiple sclerosis:
• Unilateral involvement.
• Gradual slow process.
• Secondary progressive multiple sclerosis.

ADEM - Acute Disseminated Encephalomyelitis

• <20yrs

• Monophasic

• Antecedent infection

• ON : B/L

• Spinal cord: Long segment

NMOSD (Neuromyelitis Optica Spectrum Disorder)
DEVIC'S DISEASE

• DEVIC'S DISEASE

• 20 -40 yrs

• Female: Male ratio = 3:1.

• Demyelinating disease.

• Disease is Astrocytopathy
• Damage to astrocyte foot processes causes cerebral edema and death.
• Astrocyte foot processes: 
• Do not form blood brain barrier.
• BBB → Formed by endothelium of Brain capillaries

Cause

• Can be secondary (2°) to Multiple Sclerosis

Death

• Spinal cord involvement at C3, C4, C5

• Phrenic nerve supply to diaphragm is affected.
• Causes respiratory failure.

• NOTE: In many neurological diseases
• parkinsonism, Alzheimer’s, VCJD
• death is often due to pneumonia from being bedridden and aspirating.

Antibodies:

• NMO IgG antibodies / Anti-Aquaporin-4 antibody
• Damages water channel,
• Causes cerebral edema

• Anti-MOG
• Myelin oligodendrocyte glycoprotein antibody.

Manifestation:

1. Optic neuritis
• Sudden onset blindness
• bilateral
• Increased (↑) chance of relapse
• More frequent than in Multiple Sclerosis alone
• History of recurrent Optic Neuritis
• most important to differentiate from MS

2. Longitudinal extensive transverse myelitis:
• >3 consecutive spinal segments.
• Symptoms:
• Pin, needle sensations,
• Root pain/radicular pain below level.
• Acid or boiling pain

3. Spectrum disorder manifestations:
• A: Area postrema syndrome (protracted vomiting).
• B: Brainstem syndrome (3rd cranial nerve or any other nerve palsy).
• C: Cerebral syndrome (seizures, encephalopathy).
• D: Diencephalic syndrome (hypothalamus affected)
• Hunger affected → Anorexia, Weightless
• N: Narcolepsy (damage to Reticular activating system).

NOTE

• Multiple sclerosis:
• Relapsing/remitting course,
• mostly unilateral ocular deficit.

Diagnosis criteria for NMOSD

• At least
• 1 clinical core feature + Anti aquaporin 4 antibody.

• If antibody not identified:
• 2 clinical core features + Gadolinium enhanced MRI.

• MRI:
• Optic neuritis.
• MRI spine: >3 segments involved.
• Cloud like brain lesions (parenchyma or brain stem).

Treatment:

• β-Interferon, Glatiramer: Contraindicated.

• Methylprednisolone.

• No improvement: Plasmapheresis.

Prevention:

• Immunomodulators +
• Mycophenolate, Azathioprine

• Steroids

Important Information

• Therapeutic Plasmapheresis indicated in:
• HUS.
• TTP.
• NMOSD.
• GBS

Huntington's Chorea

• Autosomal Dominant

• 50-60 years of age.

• Genetics: 
• Involves CAG repeats on the exon of chromosome number 4.

• Increased Proteins: 
• Huntington protein and ubiquitin ↑↑ in caudate nucleus

• U quit (ubiquitin) hunting (huntington protein) in kaadu (caudate)

• Atrophy of caudate nucleus.
• Frontal horn of lateral ventricles dilates.
• MRI head: Boxcar ventricle.

Note

• Corpus Callosum Lipoma
• Shows bracket calcification.
• Mnemonic:
1. C C → Brackets
2. Lip → Put brackets

Important Information

• Neurotransmitters affected:
• Dopamine: ↑↑.
• NOTE: In parkinsonism (Typical or atypical variety):
• Dopamine values are less.
• GABA: ↓↓↓
• ↓ inhibitions
• Low inhibitions and high dopamine when hunting

Callosal dysgenesis/agenesis

• Square root wave sign in cardiac catheterization finding with constrictive pericarditis

• Onion skinning, round pattern
• Mnemonic: PSM Squared

• Monckeberg's Sclerosis (CMD):
• Ca in tunica media (old age).

• First Site of Calcium Deposition:
• Mitochondria
• Exception (kidney): Basement membrane.

Brain lesions with calcification

1. Craniopharyngioma

2. Oligodendroglioma

3. Meningioma.

4. Congenital CMV
• Periventricular calcification

5. Congenital Toxoplasmosis
• Cerebral calcification

6. Neurocysticercosis.

• Mnemonic: Brain calcifiy () → when Old (Oligodendroglioma) → start saying Meaningful (Meningioma) Crap (Craniopharyngioma)

Tuberous Sclerosis Complex (TSC)

• Also called:
• Bourneville's disease
• Epiloia (Epilepsy, Low intelligence, Adenoma sebaceum)

• Autosomal dominant inheritance.

• Gene defect:
• TSC1 (Chromosome 9).
• Hamartin gene
• TSC2 (Chromosome 16).
• Tubulin gene

• Chromosome: 9 and 16

• Features (mnemonic: HAMARTOMAS):
• Hamartoma (general)
• Wunderlich Syndrome:
• Massive retroperitoneal hemorrhage
• Lenk's triad: mass, hypotension, flank pain
• Mnemonic: Wonder (Wunderlich) that fat occur in kidney
• Wonder Land → Wunder Lenk
• Adenoma sebaceum
• Mental retardation
• Ash leaf spots
• Rhabdomyoma
• Tubers
• Optic hamartomas
• Mitral regurgitation
• Astrocytoma
• Seizures

Presentation:

1. Cutaneous lesion +

2. Epileptic
• CNS:
• 1st year: Infantile spasm.
• Management: Vigabatrin.
• Leads to mental retardation.
• After 1 year: Focal seizures.
• Management: Carbamazepine (lifelong).
• MRI brain
• Subependymal astrocytoma (potato-like).

Important skin features:

• Mnemonic: Hamara (Hamartomatous) Ashley (Ash leef) green color (sha green) tube (tuberous sclerosis) il keri koya (koenen) de conmference (confetti) nu poi → Bougainvilla (Bourneville's disease) de kambeduth Adich (Adenoma sebaceoum) → Red papules () vann

Subependymal nodules

• Can enlarge to form SEGA (Subependymal Giant Cell Astrocytoma)

• Most common site: foramen of Monro

• Mnemonic: Tube (TS) nte thazhe nodules (Subependymal nodules) vachitt Munroe (Foramen of munro) poi → Giant (SEGA) aale kanan

Adenoma sebaceum:

• Misnomer (not related to sebaceous glands)

• Cutaneous angiofibroma / Facial Angiofibroma

• Acneiform lesion with butterfly distribution

• Red papules on cheeks, nose, nasolabial folds, and chin

• Asymptomatic

• Starts appearing at 3-4 years of age
• increases during puberty

• No Comedones, no pustules (unlike acne)

Ash leaf macules / spots:

• Early cutaneous feature at birth

• Leaf-shaped or lancet-shaped hypopigmented lesions

Shagreen patch:

• Leathery patch

• Collagenoma

• orange peel consistency

Koenen's tumors:

• Periungual tumors (periungual fibromas)

• Subungual fibroma causing nail crack

• Fleshy growth at root of nail.

• Seen along nail folds

Confetti-like macules

Gingival fibromas

Cafe au lait macules (may be present)

Systemic features:

• Hamartomas affecting:
• Neurological system
• Eyes
• Lungs
• Cardiac system
• Renal system

Important Information

• For infantile spasm:
• ACTH.

• Infantile spasm + Tuberous sclerosis:
• Vigabatrin.

• Port-wine stain in trigeminal distribution

• Leptomeningeal Angiomatosis (ipsilateral)
• cavernous angioma (vascular malformation).
• Convulsions (Focal)
• behavioural problems,
• Mental retardation

• Choroidal Hemangiomas
• Ocular complications
• ipsilateral glaucoma,
• blindness,
• congestion
• Buphthalmos

• Unilateral weakness
• d/t tumor compressing corticospinal pathway.

CT scan:

• S-shaped intracranial calcifications

• S for Sturge-Weber, S for S shaped





 

• Tram track appearance or rail road calcification
• NOTE: Also seen in
• membranoproliferative glomerulonephritis,
• bronchiectasis.

• Mnemonic: Web of storage (Sturg Weber) of Portwine factories () → connected by rail tram tracks (Tram track apearance)

• Two types: NF1, NF2.

• NF1:
• Hypertension (associated with pheochromocytoma).
• Autosomal dominant.
• Chromosome 17 defect.
• Neurological: Optic glioma.
• Cutaneous:
• 6 Café-au-lait macules (>5mm).
• Axillary/inguinal freckles.
• Pulsation of cavernous sinus is felt in eyeball (thinning of sphenoid bone).
• Lisch nodules (iris hamartoma).

• NF2:
• NF2 is located on chromosome number 22.
• Mnemonic (MISS ME):
• Multiple inherited Schwannomas
• Acoustic neuroma.
• Meningioma
• Ependymoma

• ATP Genes
1. ATP 7A → Menkes
2. ATP 7B → Wilsons
3. ATP → Rotor syndrome
• [DR → (DJ syndrome, Rotor syndrome)→ need MRP and ATP]

• Chromosome 17
• Newly 17 (NF1) yr girl tried bra for 1st (BRCA1) time
• Police caught At 17 → 17p13q → p53

• Chromosome 13
• RB gene, BRCA 2, ATP 7B
• all Betas

Neurofibromatosis Type 1 (NF1)

• Mnemonic: NF
• Newly 17 girl → she was soft with pedunculated (Neurofibromas → soft, pedunculated) boobs → she wore skin coloured () bra and red coloured () panties and button (button hole sign) in her navel hole ()
• She was dominant (AD)
• she won a house for her reckless (Von reckling house) behavious
• She got wings (sphenoid wing dysplasia)
• She want to cafe (Cafe laut) → met with 6 guys (> 6 lesions) →
• She put lens in iris (iris hamartoma) and wore a leash (Lisch nodules)
• invited as a crew (Crows sign) → to lick her axiilla (In axilla)
• Her legs got bent (Bowing of legs)
• She lost vision → Optic N glioma

• Presence of neurofibromas

• Inheritance: Autosomal dominant pattern

• Chromosome: 17

• Also called: Von Recklinghausen's disease

Features (mnemonic: CAFES):

• Cafe au lait spots:
• > 6 lesions
• > 5 mm in prepubertal individuals
• > 15 mm in postpubertal individuals

• Axillary or inguinal freckling:
• Axillary freckling also called Crowe sign

• Fibromas:
• Two or more neurofibromas OR
• One plexiform neurofibroma
• (present along the nerve in an elongated fashion)
• Neurofibroma:
• Soft, pedunculated,
• skin-colored to red-colored lesions,
• present anywhere
• Feels very soft, called button-hole sign

• Eye:
• Optic nerve glioma (m/c CNS tumor in NF - 1)
• Iris hamartomas (Lisch nodules)

• Skeletal abnormalities:
• Sphenoid wing dysplasia OR
• Leg bowing

• Additional features:
• Positive family history:
• History of NF in a first-degree relative
• CNS features:
• Epilepsy
• Low intelligence
• Malignancies:
• Dry and astrocytoma

Diagnosis:

• Two or more of these features

Neurofibromatosis Type 2 (NF-2)

Genetics and Key Feature

• Gene: Mutation in Merlin protein (also called Schwannomin)

• Chromosome: Located on chromosome 22

• Accounts for 3–4% of all neurofibromatosis cases

• Mnemonic: 22 yr old Merlin was showoff (Schwannomin)

Pathognomonic finding:

• Bilateral Vestibular Schwannoma (B/L VS) OR

• Acoustic Neuroma

• B/L ice cream cone appearance in cerebellopontine angle.
• B/L Vestibular schwannoma.

• Chromosome no. 22.

• Mnemonic: Show man () eating Ice cream () with 22 (Chr 22) year old

Diagnostic Criteria for NF-2

• Diagnosis can be made with any one of the following:
• Positive family history of NF-2 (+)
• Unilateral Vestibular Schwannoma
• Plus any of:
• Meningioma >>
• Glioma
• Neurofibroma
• Juvenile posterior subcapsular lenticular opacities

Ataxia Telangiectasia:

 

Investigations

• ↑ AFP

• ↓ IgA, IgG, and IgE

• Defects in ATM gene
• failure to detect DNA damage
• Failure to halt progression of cell cycle → mutations accumulate

• Mnemonic: Ataxic Telangiectasia Mutation gene (ATM gene)

• AGE (IgA, IgG, IgE) decreases and become fetus (AFP) → Children are ataxic → afraid of Spider (Spider angioma)

• Autosomal Recessive

• Telangiectasia:
• Dilated blood vessels.

• Ataxia:
• Spinocerebellar pathway involved.

• IgA deficiency.

• Increased risk of blood cancer.

• Characterized by:
• Triad:
• cerebellar atrophy (ataxia),
• spider angiomas (telangiectasia A),
• IgA deficiency
• Progressive neurodegeneration
• Immune system dysfunction
• Higher susceptibility to infections
• ↓ Sensitivity to radiation
• limit X-ray exposure
• Lymphopenia
• ↑ Risk of lymphoma and leukemia

Vaccines:

• Generally recommended (for protection)

• Immune response may be impaired (due to underlying immune deficiency)

• Von Hippel-Lindau (VHL) syndrome
• Defect:
• Chromosome 3p deletion (from VHL's three alphabets)
• VHL gene.
• Activate Hypoxemia Inducible Factors (HIF)
• Clear cell RCC
• SmaLL CELL lung cancer (L myc, 3p)
• Pheochromocytoma
• Cerebellar Hemangioblastoma
• Retinal hemangioblastoma
• may bleed causing vision loss
• Spinal cord hemangioblastoma
• Vascular tumour of spinal cord
• Cutaneous: Café-au-lait macules.
• Hemangioendothelioma
• Hemangioendothelioma + RCC ⇒ Paraneoplastic Polycythemia

Revise Epilepsy

SSLC / SCENE Genes

• GBS is an 
• acute onset (≤4 weeks)
• bilateral symmetrical
• inflammatory
• autoimmune polyradiculoneuropathy.

• Autoimmune Demyelination of peripheral nervous system.

• Ascending, symmetrical, flaccid paralysis.

• 7th cranial nerve is most commonly involved

• Bladder and bowel spared (if involved → transverse myelitis)

• GBS is usually post-infectious (2-3 weeks).
• A/w Campylobacter

• AIDP is most common GBS.

• Antibody: Anti GM1 Antibody.
• NOTE:
• Miller Fisher: Anti GQ1 Antibody.
• Mnemonic: Fish vangan Que nikkanam

• Brighton criteria for diagnosis.
• NOTE: Revised McDonald criteria for Multiple sclerosis.

Pathophysiology

• IgG Antibodies → Bind to Myelin/Axons → Activates complement → Macrophage invasion → Vesicular degeneration

Inciting Factors/Triggers

• Gastroenteritis/URTI (Past 4 weeks):
• Present in 60-70% of GBS cases.

• Campylobacter jejuni (Most common trigger)
• Molecular mimicry implicated.

• CMV (Cytomegalovirus)

• EBV (Epstein-Barr Virus)

• Mycoplasma

• Hep A/B

• HIV

• Zika virus

• Vaccination associated.

• C. jejuni also A/w
• IPSID- Immunoproliferative Small Intestinal Disease/Lymphoma

Features:

• Earliest sign: Distal areflexia.

• Bilateral ascending symmetrical flaccid paralysis.
• Maximum severity of 2 weeks after initial onset

• B/L atonic areflexic paraparesis (Proximal > distal) of lower limbs.

• Equal paralysis of both legs
• quadriplegia

• Neuropathic pain, particularly in the legs
• Large fibre (Aα) sensory loss.

• Truncal paralysis
• Cant sit up in the bed

• Cervical demyelination
• respiratory paralysis

• Neck floppiness.

• 7th nerve palsy (facial diplegia) → M/c CN involved

• In severe cases ➔ Respiratory failure ➔ FVC should be done to assess ventilation

Brighton Criteria for GBS

• Bilateral and flaccid limb weakness.

• Decreased/absent deep tendon reflexes in weak limbs.

• Monophasic course;
• onset 12 hours to 28 days.

• No alternative diagnosis for weakness.

• Albumino-cytological dissociation

• Nerve conduction:
• consistent with GBS (latency increased).

Prognosis

• 80% recover.
• Begins 2-4 weeks after progression ceases.

• 4-15% mortality.

Bad Prognostic Factors

• Autonomic Nervous System
• Labile hypertension (Extreme BP fluctuations).
• Postural hypotension (Orthostatic hypotension).
• Arrhythmias.
• Anhidrosis.
• Tachycardia.

Typical Electrodiagnostic Features (NCS)

• Prolonged latency.

• Decreased conduction velocity.

• Conduction block.

• Absent/prolonged F-wave & H-reflex.

• Temporal dispersion.

LP: Albumino-cytological dissociation.

• CSF cells < 50/ml

• CSF protein concentration > 60 mg/dL.

• CSF opening pressure: normal.

• Sugar: normal.

• Color: normal.

Treatment

• DOC: IV Immunoglobulins.

• Plasmapheresis → PLEX (Plasma Exchange) Therapy

• Both therapies equally effective.

• No role for steroids.

DD

• Transverse myelitis vs GBS
• Bladder/bowel involvement.
• Root pain.
• Urinary incontinence.

Comparison Table

• CIDP (Chronic Inflammatory Demyelinating Polyneuropathy):
• Chronic, >8 weeks.

Classification

• All antibodies associated are IgGs.

Facial Palsy causes summary

• Most common cause:
• Idiopathic > Traumatic

• Iatrogenic facial palsy:
• Occurs during mastoidectomy
• Mastoid segment affected

Causes of B/L facial Nerve (diplegia):

Clinical Features

• 30-year-old man presented with complaint of myoclonic jerks + dementia.

• Myoclonic jerks may be produced in response to loud sound:
• Startle myoclonus.

• History suggests consumption of poor-quality beef
• eating tainted beef/ infected beef with prions.

• Transmissible Spongiform Encephalopathy (TSE).

• Bovine spongiform encephalopathy
• Spongiform vacuolations brain
• Prion → Praani () infected a Kuru () → made it spongy (spongy vacuolations) like → we took it to congo (congo red) and Passed (PAS) it to them

Pathology

• Prion disease (prion particle - smallest infectious particle).

• Prion: Protein coat only, no DNA/RNA.

• Resistant to 121°C heat.

• Kill by 134°C for 1.5 hrs (Autoclaving)

• Source: Tainted beef

• Has a long incubation period

• Prion particles → enter the GIT → enter blood stream → cross the blood brain barrier.

• PrPC → PrPSC is the abnormal folded protein
• accumulates as β Pleated structures

• start accumulating in the cytoplasm of neurons
1. Cause neurodegeneration
• dementia
2. Abnormal firing of neurons
• results in myoclonic jerks

Manifestations:

• Myoclonic jerks
• startle myoclonus

• Dementia.

• Gait ataxia.

• Incapacitation / Bedridden.

• Death due to pneumonia in Parkinsonism, Alzheimer's, VCJD.

MRI head:

• Increased intensity of basal ganglia

• Cortical Ribboning

• Hockey stick sign → Pulvinar Nucleus of thalamus

• Hockey stick sign seen in:
• In MRI: VCJD
• In ECG: Digoxin.
• In Echo: Mitral stenosis.
• In OBG: USG Abdominal circumference

CSF Examination

• Shows protein 14.3.3

EEG Finding

• Periodic sharp wave complexes.
• Keyword in MCQ, to identify VCJD
• Mnemonic:
• Variant = Periodic
• Crude = Sharp

Important Information

• Periodic lateralized epileptiform discharge (PLED)
• is seen in HSV encephalitis.
• Mnemonic: His wife → Period late → she seizures

Prion Diseases

• Sreelankan (Gerstman Schlankler Syndrome) cannibals (Kuru ds) sleep (familial fatal insomnia)

• Variant Creutzfeldt-jakob disease.

• Classical Creutzfeldt-jakob disease.
• From Human GH Inj → Prev taken from cadaveric pituitary
• Human to human transmission
• Not todays world

• KURU Disease
• (Cannibals).
• Specifically shows Kuru's plaque.
• Positive for Congo red and PAS

• Familial fatal insomnia.

• Gerstman Schlankler Syndrome.
• Disease 4 & 5 are genetic (Chromosome 20 defect).