Neuropathology — MCQs

Neuropathology Indian Medical PG Practice Questions and MCQs

Question 21: Which of the following is not seen in CNS involvement in Wilson's disease?

A. Perivascular giant cell
B. Vacuolar degeneration of posterior column
C. Microglial nodule formation
D. Inclusion bodies (Correct Answer)

Explanation: **Explanation:** Wilson’s Disease (Hepatolenticular degeneration) is an autosomal recessive disorder caused by mutations in the **ATP7B gene**, leading to impaired biliary copper excretion and toxic accumulation in the liver, brain, and eyes. **Why "Inclusion Bodies" is the correct answer:** Inclusion bodies are not a characteristic feature of Wilson’s disease. While Wilson’s involves significant cellular changes, it does not typically manifest with viral-like or proteinaceous inclusion bodies (like Lewy bodies or Negri bodies). Instead, the hallmark cellular findings are **Alzheimer Type II astrocytes**—large cells with pale nuclei and prominent nucleoli found in the basal ganglia and cortex. **Analysis of other options:** * **Perivascular giant cells & Microglial nodules:** In advanced CNS Wilson’s disease, copper toxicity leads to tissue necrosis and cavitation, particularly in the putamen. This triggers an inflammatory response involving microglial activation, nodule formation, and the presence of multinucleated giant cells as the brain attempts to clear necrotic debris. * **Vacuolar degeneration of posterior columns:** While primarily known for basal ganglia involvement (leading to parkinsonism and wing-beating tremors), Wilson’s disease can cause widespread white matter changes. Vacuolar degeneration of the spinal cord's posterior columns can occur, mimicking features of Subacute Combined Degeneration [1]. **NEET-PG High-Yield Pearls:** * **Hallmark Astrocytes:** Alzheimer Type II astrocytes (NOT Type I). * **Brain MRI:** "Face of the Giant Panda" sign (midbrain) and "Miniature Panda" sign (pons). * **Ocular finding:** Kayser-Fleischer (KF) rings in Descemet’s membrane. * **Diagnosis:** Low serum ceruloplasmin, high 24-hour urinary copper, and increased hepatic copper content. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Manifestations Of Central And Peripheral Nervous System Disease, pp. 716-717.

Question 22: Which of the following tumors causes polycythemia due to increased erythropoietin production?

A. Cerebellar hemangioblastoma (Correct Answer)
B. Medulloblastoma
C. Ependymoma
D. Oligodendroglioma

Explanation: **Explanation:** **1. Why Cerebellar Hemangioblastoma is Correct:** Hemangioblastoma is a highly vascular, benign tumor (WHO Grade I) that most commonly occurs in the cerebellum [1]. It is a classic example of a **paraneoplastic syndrome** producer. These tumor cells can ectopically secrete **Erythropoietin (EPO)**, which stimulates the bone marrow to increase red blood cell production, leading to **secondary polycythemia**. This association is a high-yield diagnostic clue in clinical vignettes. **2. Why Other Options are Incorrect:** * **B. Medulloblastoma:** This is a highly malignant (WHO Grade IV) embryonal tumor found in the posterior fossa of children [1]. It does not have endocrine or EPO-secreting activity. * **C. Ependymoma:** These tumors arise from the lining of the ventricles or central canal of the spinal cord [1]. While they can occur in the posterior fossa, they are not associated with polycythemia. * **D. Oligodendroglioma:** These are cortical tumors characterized by "fried-egg" appearance and "chicken-wire" calcifications. They do not produce EPO. **3. NEET-PG High-Yield Pearls:** * **Von Hippel-Lindau (VHL) Disease:** Approximately 25% of hemangioblastomas are associated with VHL syndrome (Chromosome 3p) [1]. If a patient has a cerebellar hemangioblastoma, always screen for **Renal Cell Carcinoma (RCC)** and **Pheochromocytoma**. * **Other EPO-secreting tumors (The "Potentially Really High Erythropoietin" mnemonic):** * **P**heochromocytoma * **R**enal Cell Carcinoma (Most common) * **H**epatocellular Carcinoma * **E**mangioma (Hemangioblastoma) * **U**terine Fibroids (rarely) * **Histology:** Look for "Stroma cells" with vacuolated, lipid-rich cytoplasm and a dense network of thin-walled capillaries [1]. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Manifestations Of Central And Peripheral Nervous System Disease, pp. 726-727.

Question 23: Amyloid present in cerebral lesions of Alzheimer's disease is which type?

A. L
B. AA
C. Ab (Correct Answer)
D. b-microglobulin

Explanation: **Explanation:** The correct answer is **Aβ (Amyloid beta)**. In Alzheimer’s Disease (AD), the characteristic extracellular neuritic (senile) plaques are composed of Aβ amyloid [1], [3]. This peptide is derived from the proteolysis of **Amyloid Precursor Protein (APP)**, a transmembrane protein [2]. When APP is cleaved by **β-secretase** and **γ-secretase** (instead of the non-amyloidogenic α-secretase), it produces Aβ peptides, particularly the Aβ42 isoform, which is highly prone to aggregation and neurotoxicity [2]. **Analysis of Incorrect Options:** * **AL (Amyloid Light Chain):** Derived from immunoglobulin light chains produced by plasma cells. It is associated with **Primary Systemic Amyloidosis** and Multiple Myeloma. * **AA (Amyloid Associated):** Derived from Serum Amyloid-Associated (SAA) protein, an acute-phase reactant. It is seen in **Secondary Amyloidosis** resulting from chronic inflammation (e.g., Tuberculosis, Rheumatoid Arthritis). * **β2-microglobulin (Aβ2M):** This type of amyloid is typically seen in patients on **long-term hemodialysis**, as the protein cannot be filtered through dialysis membranes, leading to deposits in joints and ligaments (Carpal Tunnel Syndrome). **High-Yield Clinical Pearls for NEET-PG:** * **Intracellular Finding:** While Aβ is extracellular, AD also features **Neurofibrillary Tangles (NFTs)**, which are intracellular aggregates of hyperphosphorylated **Tau protein** [1], [4]. * **Genetics:** Mutations in *APP* (Chr 21), *Presenilin 1* (Chr 14), and *Presenilin 2* (Chr 1) lead to early-onset AD [2]. The **ApoE4** allele increases the risk of late-onset AD. * **Staining:** Amyloid shows **apple-green birefringence** under polarized light when stained with **Congo Red**. * **Cerebral Amyloid Angiopathy (CAA):** Aβ can also deposit in the walls of cerebral vessels, increasing the risk of lobar hemorrhage [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Central Nervous System, pp. 1292-1294. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Central Nervous System, pp. 1290-1292. [3] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Manifestations Of Central And Peripheral Nervous System Disease, pp. 719-720. [4] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Central Nervous System, pp. 1292-1293.

Question 24: A 42-year-old man presents with worsening involuntary jerky movements, depression, and progressive dementia. He dies within several years, and autopsy reveals bilateral atrophy of the caudate nuclei. What is the basic abnormality involved in this individual's disease process?

A. Acquired enzyme deficiency
B. Slow virus infection
C. Triple repeat mutation (Correct Answer)
D. DNA repair defect

Explanation: ### Explanation The clinical presentation of **chorea** (involuntary jerky movements), **psychiatric symptoms** (depression), and **dementia**, combined with the pathognomonic autopsy finding of **bilateral caudate nucleus atrophy**, confirms a diagnosis of **Huntington Disease (HD)**. **1. Why "Triple Repeat Mutation" is correct:** Huntington Disease is an autosomal dominant neurodegenerative disorder caused by an unstable expansion of **CAG (cytosine-adenine-guanine) trinucleotide repeats** [2] in the *HTT* gene on chromosome 4. This "triple repeat mutation" leads to an abnormally long polyglutamine tract in the huntingtin protein, resulting in toxic gain-of-function that causes neuronal death, specifically in the striatum (caudate and putamen) [1]. **2. Why other options are incorrect:** * **Acquired enzyme deficiency:** This describes conditions like organophosphate poisoning or certain metabolic toxicities, not a progressive genetic neurodegenerative disease. * **Slow virus infection:** This refers to conditions like Subacute Sclerosing Panencephalitis (SSPE) or Creutzfeldt-Jakob Disease (prion). While these cause dementia, they do not typically present with isolated caudate atrophy or chorea. * **DNA repair defect:** This is the hallmark of **Ataxia-Telangiectasia** or Xeroderma Pigmentosum. While Ataxia-Telangiectasia involves cerebellar atrophy and movement issues, it presents in childhood with telangiectasia and immunodeficiency. **Clinical Pearls for NEET-PG:** * **Anticipation:** HD exhibits "anticipation," where the disease presents earlier and more severely in successive generations, especially when inherited from the **father** (due to expansion during spermatogenesis). * **Neurotransmitters:** There is a characteristic **decrease in GABA and Acetylcholine**, and an **increase in Dopamine** in the striatum. * **Imaging/Gross Pathology:** "Boxcar ventricles" (enlargement of the lateral ventricles due to caudate atrophy). * **CAG Repeat Diseases:** Remember the mnemonic "Try (Trinucleotide) **Hunting** for **My** **Fried** **Eggs** (Huntington’s, Myotonic Dystrophy, Friedreich’s Ataxia, Fragile X). **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Central Nervous System, pp. 1299-1300. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, p. 177.

Question 25: What type of inclusion bodies are seen in progressive myoclonic epilepsy?

A. Buschino bodies
B. Lewy bodies
C. Hirano bodies
D. Lafora bodies (Correct Answer)

Explanation: **Explanation:** **Lafora bodies** are the hallmark pathological finding in **Lafora Disease**, a severe form of autosomal recessive **progressive myoclonic epilepsy**. These are round, eosinophilic, PAS-positive cytoplasmic inclusion bodies composed of **polyglucosans** (abnormal glycogen polymers). They are typically found in the neurons of the cerebral cortex, thalamus, and brainstem, but can also be identified in sweat gland duct cells via skin biopsy, making it a high-yield diagnostic tool. **Analysis of Incorrect Options:** * **Buschino bodies:** These are not a recognized entity in neuropathology; this is likely a distractor. (Note: *Bunina bodies* are eosinophilic inclusions seen in Amyotrophic Lateral Sclerosis). * **Lewy bodies:** These are alpha-synuclein inclusions found in the substantia nigra in **Parkinson’s disease** and cortical neurons in **Lewy Body Dementia**. * **Hirano bodies:** These are actin-rich, eosinophilic, rod-like inclusions found primarily in the hippocampus of patients with **Alzheimer’s disease** and normal aging. **Clinical Pearls for NEET-PG:** * **Lafora Disease Presentation:** Characterized by the triad of myoclonus, rapidly progressive dementia, and seizures, typically starting in adolescence. * **Genetics:** Mutations in *EPM2A* (laforin) or *EPM2B* (malin) genes. * **Diagnostic Tip:** If a question mentions "PAS-positive inclusions in a skin biopsy" for a patient with seizures, the answer is almost always Lafora bodies. * **Other Polyglucosan Bodies:** Corpora amylacea (seen in aging brains) are also polyglucosan bodies but are extracellular and lack the clinical severity of Lafora bodies.

Question 26: What is true about meningiomas?

A. More common in men
B. 50% are malignant
C. 95% cure rate following treatment (Correct Answer)
D. Arise from the arachnoid layer

Explanation: **Meningiomas** are the most common primary intracranial tumors, typically arising from the **arachnoid cap cells** of the arachnoid villi. [1] ### **Explanation of the Correct Option** * **Option C (95% cure rate following treatment):** Most meningiomas are slow-growing, benign (WHO Grade 1) lesions. Because they are extra-axial (located outside the brain parenchyma) and well-circumscribed, complete surgical resection (Simpson Grade I) often leads to a permanent cure [1]. The 5-year survival rate for benign meningiomas is exceptionally high, often cited around 92-95%. ### **Analysis of Incorrect Options** * **Option A:** Meningiomas are significantly **more common in women** (female-to-male ratio of approximately 2:1 or 3:1). This is partly due to the presence of estrogen and progesterone receptors on the tumor cells [1]. * **Option B:** The vast majority (approx. 85-90%) of meningiomas are **benign** (WHO Grade 1) [1]. Malignant (anaplastic) meningiomas are rare, accounting for only about 1-3% of cases. * **Option D:** While they are associated with the arachnoid, they specifically arise from **arachnoid cap cells**, not the entire "arachnoid layer" generally. (Note: In many exams, "arachnoid cap cells" is the more precise anatomical origin required). ### **High-Yield Clinical Pearls for NEET-PG** * **Risk Factors:** Prior radiation exposure is the most well-established environmental risk factor. * **Genetics:** Loss of **NF2 gene** on chromosome 22q is the most common genetic alteration [1]. * **Histology:** Look for **Psammoma bodies** (laminated calcifications) and **whorled patterns** of spindle cells [1]. * **Radiology:** Characterized by the **"Dural Tail Sign"** on contrast-enhanced MRI [1]. * **Common Locations:** Parasagittal region, olfactory groove, and sphenoid wing. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Central Nervous System, pp. 1316-1317.

Question 27: Which area of the brain most commonly undergoes atrophy in Alzheimer's disease?

A. Temporoparietal (Correct Answer)
B. Parieto-occipital
C. Frontoparietal
D. Temporo-occipital

Explanation: Alzheimer’s Disease (AD) is characterized by a predictable pattern of neurodegeneration. The atrophy typically begins in the **medial temporal lobe** (specifically the hippocampus and entorhinal cortex), which explains the early loss of short-term memory [1]. As the disease progresses, the atrophy spreads to the **lateral temporal and parietal association areas** [1]. **1. Why Temporoparietal is Correct:** The hallmark of AD is the accumulation of Amyloid-beta plaques and Tau-tangles [3]. These changes predominantly affect the **Temporoparietal junction**. On imaging (MRI) and gross pathology, this manifests as symmetrical cortical atrophy, compensatory ventricular enlargement (*hydrocephalus ex vacuo*), and "knife-edge" thinning of the gyri in these specific regions [1]. Functional imaging (PET scans) also shows characteristic hypometabolism in the temporoparietal cortex. **2. Why other options are incorrect:** * **Parieto-occipital / Temporo-occipital:** The primary visual cortex (occipital lobe) is remarkably spared in typical Alzheimer’s disease until the very terminal stages. * **Frontoparietal:** While the frontal lobe can undergo atrophy in late-stage AD, primary frontal involvement is the hallmark of Frontotemporal Dementia (Pick’s Disease), characterized by early personality changes rather than memory loss [2]. **High-Yield Clinical Pearls for NEET-PG:** * **Microscopic Hallmarks:** Extracellular **Neuritic (Senile) plaques** (Aβ42) and Intracellular **Neurofibrillary tangles** (Hyperphosphorylated Tau) [1]. * **Hirano Bodies:** Eosinophilic, actin-rich inclusions found in hippocampal pyramidal cells. * **Genetics:** Early-onset is linked to **APP, PSEN1, and PSEN2** mutations; Late-onset is linked to the **ApoE4** allele [1]. * **Neurotransmitter:** Significant decrease in **Acetylcholine** due to atrophy of the Nucleus Basalis of Meynert. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Manifestations Of Central And Peripheral Nervous System Disease, pp. 719-721. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Central Nervous System, pp. 1294-1295. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Central Nervous System, pp. 1289-1290.

Question 28: Which protein is primarily associated with Alzheimer's disease?

A. Apolipoprotein E gene (Correct Answer)
B. Presenilin II
C. Amyloid precursor protein
D. All of the above

Explanation: **Explanation:** Alzheimer’s Disease (AD) is characterized by the accumulation of Amyloid-beta (Aβ) plaques and Tau tangles [2], [4]. While multiple genes are involved in its pathogenesis, the distinction lies between **sporadic (late-onset)** and **familial (early-onset)** forms [1]. **Why Option A is correct:** **Apolipoprotein E (ApoE)**, specifically the **ε4 allele**, is the most significant genetic risk factor for the **sporadic form** of Alzheimer’s, which accounts for >95% of all cases. The ApoE protein is involved in the clearance and aggregation of Aβ; the ε4 isoform is less efficient at clearing these peptides, leading to increased plaque deposition. **Why other options are incorrect:** * **Presenilin II (PSEN2):** Mutations in PSEN1 (Chr 14) and PSEN2 (Chr 1) are associated with **familial** AD [1]. While they cause the disease, they represent <5% of total cases [4]. * **Amyloid Precursor Protein (APP):** Located on Chromosome 21, mutations in APP also lead to early-onset familial AD [1], [3]. (Note: This is why Down Syndrome patients develop AD early) [1]. * **Option D:** While all these proteins are "associated" with AD, in the context of standard medical examinations, if a single "primary" association is sought without specifying "familial," the focus is on the most common genetic risk factor in the general population (ApoE). **High-Yield Clinical Pearls for NEET-PG:** * **ApoE ε2:** Protective against Alzheimer’s. * **ApoE ε4:** Increases risk and decreases age of onset (Sporadic). * **PSEN1:** Most common cause of Familial AD. * **Hirano Bodies:** Eosinophilic, actin-rich inclusions found in the hippocampus of AD patients. * **Choline Acetyltransferase (ChAT):** Levels are significantly decreased in the nucleus basalis of Meynert [2]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Central Nervous System, pp. 1290-1292. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Manifestations Of Central And Peripheral Nervous System Disease, pp. 719-722. [3] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Manifestations Of Central And Peripheral Nervous System Disease, pp. 720-721. [4] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Central Nervous System, pp. 1289-1290.

Question 29: An immunocompromised person presents with a history of seizures and an MRI revealing a temporal lobe lesion. Brain biopsy results showed multinucleated giant cells with intranuclear inclusions. What is the most probable cause of the lesion?

A. Hepatitis C virus
B. Herpes simplex virus (Correct Answer)
C. Listeria monocytogenes
D. Coxsackievirus

Explanation: ### Explanation **Correct Answer: B. Herpes simplex virus (HSV)** The clinical presentation and histopathology are classic for **Herpes Simplex Encephalitis (HSE)**, typically caused by HSV-1. * **Anatomical Localization:** HSV has a unique predilection for the **temporal lobes** and orbital surfaces of the frontal lobes [1]. This often manifests clinically as seizures, olfactory hallucinations, or personality changes [2]. * **Histopathology:** The hallmark of HSV infection is the presence of **Cowdry Type A intranuclear inclusion bodies** [1]. These are eosinophilic, droplets-like masses surrounded by a clear halo. The virus also induces cell-to-cell fusion, leading to the formation of **multinucleated giant cells** [1]. --- ### Why the other options are incorrect: * **Hepatitis C virus:** This is primarily a hepatotropic virus. While it can cause cryoglobulinemia-related vasculitis or "brain fog," it does not cause acute necrotizing temporal lobe lesions or Cowdry A inclusions. * **Listeria monocytogenes:** This is a gram-positive bacterium that typically causes meningitis or rhombencephalitis (brainstem involvement) in immunocompromised patients. It would show neutrophilic infiltration or abscess formation, not intranuclear inclusions. * **Coxsackievirus:** A common cause of viral (aseptic) meningitis [3]. It typically presents with diffuse meningeal inflammation rather than focal temporal lobe destruction and lacks the specific inclusion bodies seen in HSV. --- ### High-Yield NEET-PG Pearls: * **Gold Standard Diagnosis:** PCR of the CSF for HSV DNA is the diagnostic test of choice. * **Imaging:** MRI is more sensitive than CT; look for "hyperintensity" in the temporal lobes on T2/FLAIR sequences [2]. * **Treatment:** Immediate IV **Acyclovir** is life-saving; do not wait for biopsy results. * **Pathology Keyword:** "Hemorrhagic necrotizing encephalitis" is the classic macroscopic description of HSV-affected brain tissue [2]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Infectious Diseases, pp. 365-366. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Central Nervous System, p. 1278. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Central Nervous System, pp. 1274-1275.

Question 30: A man presents with multiple painless swellings all over the body and coffee-brown patches on his trunk. What is the likely diagnosis?

A. Multiple lipomas
B. Multiple neurofibromas (Correct Answer)
C. Melanoma
D. Sebaceous cysts

Explanation: **Explanation:** The clinical presentation of multiple painless swellings combined with coffee-brown patches is a classic description of **Neurofibromatosis Type 1 (NF1)**, also known as von Recklinghausen’s disease. **1. Why Multiple Neurofibromas is Correct:** The "coffee-brown patches" are **Café-au-lait spots**, which are the earliest cutaneous manifestations of NF1. The "multiple painless swellings" represent **neurofibromas**, which are benign nerve sheath tumors composed of a mixture of Schwann cells, fibroblasts, and perineural cells [1]. These tumors often have a characteristic "buttonhole sign" (invagination into the skin when pressed). **2. Why Other Options are Incorrect:** * **Multiple Lipomas:** While these are painless subcutaneous swellings, they are not associated with Café-au-lait spots. They are composed of mature adipocytes and usually feel softer and more lobulated. * **Melanoma:** This is a malignant tumor of melanocytes. It typically presents as a single, enlarging, pigmented lesion with irregular borders (ABCDE criteria), not as multiple generalized swellings and patches. * **Sebaceous Cysts:** These are common skin cysts filled with keratin. They usually feature a central punctum and are not associated with systemic pigmentary changes. **3. High-Yield Clinical Pearls for NEET-PG:** * **Genetics:** NF1 is autosomal dominant; the gene is located on **Chromosome 17** (codes for Neurofibromin, a negative regulator of the RAS pathway). * **Lisch Nodules:** Pigmented iris hamartomas (pathognomonic for NF1). * **Optic Glioma:** The most common CNS tumor associated with NF1. * **Diagnostic Criteria:** Requires 2 or more of: ≥6 Café-au-lait spots, ≥2 neurofibromas (or 1 plexiform), axillary/inguinal freckling (**Crowe sign**), optic glioma, Lisch nodules, or specific bony lesions. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Peripheral Nerves and Skeletal Muscles, pp. 1249-1250.

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Cellular Pathology of the Nervous System

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Cerebrovascular Diseases

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Trauma to the Central Nervous System

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Infections of the Nervous System

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Demyelinating Diseases

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Neurodegenerative Diseases

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CNS Tumors

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Peripheral Nerve Disorders

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Neuromuscular Junction Diseases

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Congenital and Developmental Disorders

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