Essential Features: Myopathic Versus Neurogenic Changes Definition Myopathic changes are seen in disorders that primarily affect muscle Neurogenic changes in skeletal muscle result from disorders of innervation: peripheral nerve, motor neuron disease, or neuromuscular junction Clinical Features Epidemiology Depends on the specific disease process Presentation Myopathies usually present with the following: Proximal muscle weakness, usually symmetric Malaise and fatigue No sensory complaints or paresthesias Atrophy and…

Basic Reactions in Peripheral Nerve Disorders Definition Pathologic changes seen in any component of the peripheral nerve Clinical Features Epidemiology Peripheral nerve disorders are common conditions affecting approximately 2.4% of the population Prevalence increases with age to up to 8% of the population Presentation Altered sensation including numbness, pain, and paresthesia if a sensory nerve is involved Weakness (distal more than proximal) if a motor nerve…

Neuronal Storage Diseases Definition Autosomal recessive lysosomal storage diseases primarily affecting neurons/gray matter (“poliodystrophies”) (the leukodystrophies are considered in the next chapter) Representative examples of gangliosidoses are presented here Clinical Features Epidemiology Specific enzyme deficiencies that cause impaired removal of a metabolite (such as gangliosides or sphingolipids) and accumulation in neurons Gangliosidoses: autosomal recessive mutations in genes such as HEXA, HEXB, or GM2A genes, resulting in…

Wernicke-Korsakoff Disease Definition A complex of neurologic deficits associated with vitamin B 1 (thiamine) deficiency Clinical Features Epidemiology Prevalence: 1% to 3% Age: onset ranges from 30 to 70 years Thiamine Dietary sources: pork and whole grains Absorbed from duodenum, converted to thiamine pyrophosphate (TPP) TPP: important cofactor in breakdown of sugars and amino acids In central nervous system: affects myelin sheath and glucose metabolism, neurotransmitter…

Toxic Leukoencephalopathy Definition General term used here to describe a white matter demyelinating/destructive process caused by innumerable therapeutic and toxic agents Clinical Features Epidemiology May affect all ages, overall prevalence unknown Abused substances Inhalants (glue, spray paint, etc.) Cocaine, heroin, “ecstasy” Heroin vapor inhalation (“chasing the dragon”) Ethanol: greater white matter loss than nonabusers over time Chemotherapy (especially intrathecal methotrexate) Whole brain irradiation (up to 28%…

Definition Acute, inflammatory demyelinating disease, which presents as a solitary, large (>2 cm) focus of demyelination within a cerebral hemisphere with associated edema that may simulate neoplasm or abscess; synonyms include tumefactive multiple sclerosis lesions, tumor-like demyelinating lesions, and demyelinating pseudotumors Clinical Features Epidemiology Rare (but must be distinguished from tumor because of marked differences in therapy) Affects all ages; range 2 to 71 years old (average…

Definition Hyperacute (fulminant) form of acute disseminated encephalomyelitis with perivascular hemorrhages, myelin destruction, necrotizing venulitis, and scattered ischemic lesions throughout the CNS Clinical Features Epidemiology Rare, sporadic disease Occurs in all ages but more common in childhood No gender predilection You’re Reading a Preview Become a Clinical Tree membership for Full access and enjoy Unlimited articles Become membership If you are a member. Log in here

Definition Acute demyelinating inflammatory disorder characterized by perivascular (especially perivenular) myelin loss that is widely distributed throughout the brain and spinal cord and only affects the central nervous system (CNS); a monophasic disorder; occurs most often in children Clinical Features Epidemiology Incidence: 0.4 to 0.8 per 100,000 Rarely associated with vaccinations: 0.1 to 0.2 per 100,000 May occur after viral infections: measles, mumps, rubella, varicella, vaccinia,…

Multiple Sclerosis Definition Autoimmune, chronic inflammatory, demyelinating disease of the central nervous system; intermittent episodic neurologic impairments of varying severity caused by multiple demyelinating lesions, often of different ages Key pathologic features: Perivenular inflammation with primary myelin loss and relative sparring of axons—early in disease Significant axonal destruction as disease progresses Demyelination and axonal injury confined to CNS Subtypes include relapsing-remitting, primary progressive, secondary progressive, and…

Definition Vascular dementias are a group of chronic progressive dementing disorders resulting from hypoperfusive, occlusive, or hemorrhagic cortical or subcortical infarcts Binswanger disease (subcortical vascular dementia) refers to a widespread small-vessel disease affecting the deep white matter usually associated with systemic hypertension with atherosclerosis and arteriolosclerosis Clinical Features Epidemiology Vascular dementias are the second most common cause of senile dementia Usually presents in patients >60 years…

Neurodegeneration with Brain Iron Accumulation Type 1 (NBIA 1) Definition Progressive neurodegenerative disease characterized clinically by extrapyramidal symptoms with dementia and by the presence of iron accumulation and axonal spheroids within the globus pallidus and substantia nigra histologically Previously called: Hallervorden–Spatz disease Clinical Features Epidemiology Rare, sporadic or autosomal recessive inherited disease Usually affects adolescents, age range: 7 to 15 years old; infant and adult presentations…

Huntington Disease Definition Autosomal dominant neurodegenerative disease characterized clinically by choreiform movements, psychiatric symptoms, and dementia and genetically by expansion of the trinucleotide (CAG) repeat in the HD gene Clinical Features Epidemiology Age range: 2 to 85 years (mean age: 40) Incidence: 2 to 4.7 per 1 million individuals/year Prevalence: 5 to 8 per 100,000 individuals No gender predominance Autosomal dominant disorder caused by expanded CAG…

Definition Progressive neuromuscular disease characterized by degeneration of upper and lower motor neurons resulting in progressive skeletal muscle wasting and weakness leading to respiratory failure and death; ALS subtypes: primary lateral sclerosis (mainly upper motor disease) and progressive muscular atrophy (mainly lower motor disease); synonymous with motor neuron disease Clinical Features Epidemiology Incidence: 2 per 100,000 individuals/year; prevalence of about 5 per 100,000 individuals Mean age…

Parkinson's Disease Definition Progressive neurodegenerative disease characterized clinically by movement abnormalities including the triad of resting tremor, bradykinesia, and cogwheel rigidity with histologic findings of pigmented neuron loss within the substantia nigra and elsewhere Presence of α-synuclein immunoreactive Lewy bodies in affected areas “Brain stem-predominant,” “neocortical,” “limbic,” and “amygdala-predominant” types are now recognized within the spectrum of Lewy body disorders Synonyms: idiopathic parkinsonism, paralysis agitans, shaking…

Definition Progressive neurodegenerative disorders presenting with behavioral or language abnormalities FTLD with motor neuron disease (FTLD-MND)—cognitive dysfunction with the following: Clinical features of motor neuron disease or Ubiquitin-immunoreactive, tau-negative inclusion bodies within motor neurons histologically (with or without symptoms of MND) FTLD with ubiquitin-only-immunoreactive neuronal changes (FTLD-U)—cognitive dysfunction with the following: Ubiquitin-immunoreactive, tau-negative inclusions No clinical/histologic evidence of MND Clinical Features Epidemiology No gender predilection Age…

Corticobasal Degeneration (Rebeiz Disease) Definition Sporadic neurodegenerative disease characterized clinically by progressive asymmetrical involuntary movements, akinetic-rigid parkinsonism, symptoms of upper motor neuron dysfunction (dysarthria, aphasia), and variable dementia; pathologic findings are atrophy of superior frontal lobes, rostral parietal lobes, basal ganglia, and substantia nigra with widespread neuronal and glial tau inclusions Clinical Features Epidemiology Rare, idiopathic disease Affects adults in sixth to eighth decades (mean age…

Definition A neurodegenerative disorder; most frequent cause of dementia in adults—pathologically characterized by variable cerebral atrophy with neuritic (“senile”) plaques and neurofibrillary tangles Clinical Features Epidemiology Majority of Alzheimer's disease (AD) cases are sporadic, affecting adults usually older than 60 (mean age 80) Incidence increases with advancing age; 1 in 100 individuals/year between 70 to 80 years old and 2 in 100 individuals/year for 80+ years…

Prion-Related Diseases (Overview) Definition Transmissible spongiform encephalopathies caused by misfolded prion proteins Clinical Features Epidemiology Prion disease: first identified in sheep (scrapie) Later identified in elk, deer, mink, large felines Cellular PrP glycoprotein (PrPc—normal protein of unknown function) PRNP gene: chromosome 20p13 Expressed in most human tissues Neurons: contain highest levels Tertiary structure: 40% alpha-helices, 3% beta-pleated sheets PrP scrapie (PrPSc—abnormally folded form) PrPc converted to…