Table 2.70 MRI findings of metabolic dis- orders and some neurodegenerative dis- orders (729) Disorders mainly affecting the white matter of the brain (leukodystro- phies): Disorders of amino acid metabolism Lysosomal disorders and other stor- age diseases: –Metachromatic leukodystrophy –Alexander disease –Krabbe’sgloboid cell leukodystro- phy –Degenerative diffuse sclerosis of neutral lipid type –Pelizaeus-Merzbacher disease –Batten-Kufsdisease –Adrenoleukodystrophy –Diffusecerebral sclerosis (Schilder’s disease, encephalitis periaxialis dif- fusa) Spongiform degeneration of the ner- vous system (Canavan’s disease) Disorders mainly affecting the gray matter of the brain: Tay-Sachs disease and other lipidoses Hurler syndrome and other muco- polysaccharidoses (325) Mucolipidoses and fuscinoses Glycogen storage diseases Disorders affecting both white and gray matter: Leigh syndrome Mitochondrial encephalomyopathies (p. 902) Zellweger syndrome and other peroxi- somal disorders Disorders mainly affecting the basal ganglia (423): Wilson’s disease Fahr’s disease Pantothene kinase-associated neuro- degeneration (formerly Hallervorden- Spatz disease) (30, 829) Huntington’s disease Table 2.71 Lysosomal and other storage diseases affectingthenervous system Lipidoses: G M2 gangliosidoses G M1 gangliosidoses Fabry’s disease (angiokeratoma corporis diffusum) Gaucher’sdisease Niemann-Pick disease Farber’s lipogranulomatosis Wolman’s disease Refsum’s disease Cerebrotendinous xanthomatosis Neuronal ceroid lipofuscinosis Leukodystrophies: Metachromatic leukodystrophy Krabbe’s globoid cellleukodystrophy Mucopolysaccharidoses Mucolipidoses oclonus and generalized seizures in the first few months of life, followed by blindness, decorticate posturing, and death at 3–5 years. The diagnosis is made either by enzyme assay or by direct DNA analysis (the preferred method). In both Tay-Sachs disease and Sandhoff disease,aclinicallysimi- lar disorder affecting non-Jewish in- fants, a characteristic cherry-red spot is seen on the macula of the retina. Adult fo rms of hexosaminidase defi- ciency lead to dementia, s pasticity, ataxia, and muscular atrophy, or else to motor ne uron di sease, as seen in the Kugelberg-Welander and Aran- Duchenne syndromes. MRI reveals T2 hyperintensity of the basal ganglia and cerebellar cortical atrophy (913, 1042). The G M1 gangliosidoses. These disor- ders are due to a deficiency of galac- tosidase. They clinically resemble 288 2DiseasesMainlyAffecting the Brain and its Coverings Mumenthaler, Neurology © 2004 Thieme All rights reserved. Usage subject to terms and conditions of license. Tay-Sachs disease (1 041) and, like it, may b e diagnosed by enzyme assay or by direct DNA analysis. Fabry disease (angiokeratoma corpo- risdiffusum) (500). This X-linked dis- order affects the skin, kidneys, and blood vessels as well as the periph- eral and autonomic nervous system. Adeficiencyofalpha-galactosidase causes intracellular deposition of tri- hexosylceramide. The symptoms and signs arise either because of the pri- mary cellular involvement or because of vascular compromise. The initial manifestations usually appear in childhood or adolescence and consist of burning pains in the extremities, which are particularly severe in warm weather, bu t respond to diphenylhy- dantoin. Sweating is lost soon after- ward. Maculopapular, reddish-purple skin lesions appear, and, in the third or fourth decade of life, kidney failure occurs. Stroke and acute vestibular dysfunction are also common. A mild form of the disease may occur in fe- male carriers of the gene. Gaucher’s disease. This autosomal re- cessive disorder is due to glucocereb- rosidase deficiency, which results in accumulation of glucocerebroside. It occurs in juvenile and adult neuronal forms, as well as an adult nonneuro- nal form. In the juvenile form, devel- opmental delay is evident in the first few months of life, and affected chil- dren die before their second birthday. The adult neuronal form causes psy- chosis, dementia, myoclonus, gener- alized seizures, akathisia, supranu- clear gaze palsy, bulbar signs, spastic- ity, and polyneuropathy, while the nonneuronal form causes splenomeg- aly, thrombocytopenia, bone erosion, and bone pain. Characteristic foam cells (“Gaucher cells”) are found in the bonemarrow,andtheenzyme deficiency can be detected in the leu- kocytes. Enzyme replacement (intra- venous infusion of recombinant or human placental glucocerebrosidase) is an ef fective, though expensive form of treatment (67). Niemann-Pick dise ase. Adeficiencyof acid sphingomyelinase (ASM) under- lies both Type A and Type B Niemann-Pick disease. These two dis- orders represent opposite ends of a spectrum of disease, in which pa- tients with lower levels of ASM activ- ity become ill earlier, have more se- vere neu rologic involvement, and die at an earlier age. The inheritance pat- tern is autosomal recessive, and the responsible genetic defect lies on chromosome 18 (169). In Type A dis- ease, progressive encephalopathy is manifest as dementia, spasticity, ataxia, and generalized seizures, and results in death by the age of 2 years. Accompanying findings include a cherry-red spot on the retinal macula (in some cases) and hepatospleno- megaly. In Type B disease, organo- megaly and respiratory disturbances are the most prominent clinical fea- tures, and patients may survive into adolescence or adulthood. Adult -onset Niemann-Pick disease (Types C, D, and E according to the current nomenclature) is a different disease, due toadefectofcholester ol metabolism; ASM activity may be secondarily impaired. Hepatospleno- megaly is a prominent feature, and foam cells are found in the bone mar- row and liver, as in Gaucher’s disease. Aschizophrenia-like psychosis may be the presenting sign (250). Type A or B disease may be diagnosed by measurement of ASM activity in Cerebral Metabolic Disorders 289 Mumenthaler, Neurology © 2004 Thieme All rights reserved. Usage subject to terms and conditions of license. leukocytes, or by DNA analysis. T ype Cdiseaseis generally diagnosed by specialized biochemical testing of fi- broblasts obtained by skin biopsy. Refsum’s disease (heredopathia atac- tica polyneuritiformis) (783). Ref- sum’s disease is unusual in that it in- volves storage of a substance derived from the diet. A deficiency of phytanic acid alpha-dehydrogenase leads to ac- cumulation of phytanic acid in the tissues of the body, particularly the liver and kidneys. The first signs of ill- ness may appear in childhood or as late as middle age. The most promi- nent neurologic abnormalities are night blindness secondary to retinitis pigmentosa, sensorineural deafness, polyneuropathy, and ataxia (both ax- ial and appendicular). Psychiatric manifestations may also be seen. The serum phytanic acid level is elevated, and the enzyme defect may be d em- onstrated in fibroblasts. The patients’ condition improvesonprovision of a low-phytanic-aciddiet,andplasm- apheresis can also be helpful (445, 907). Cerebrotendinous xanthomatosis (cholestanol storage disease) (76). This autosomal recessive disorder is due to an anomaly of bile acid syn- thesis which results in the accumula- tion of cholestanol in the plasma and brain, as well as the formation of xan- thomata of tendon sheaths (typically on the Achilles tendon) and lungs. Al- though the xanthomata contain cho- lesterol, the serum cholesterol level is usually not elevated. Mental retarda- tion may begin early, but the charac- teristic clinical picture, with xantho- mata, cataracts, progressive spastic- ity, and ataxia, does not develop until adolescence or later.Polyneuropathy and muscle atrophy may also be se en. Dementia may develop in adulthood, and severe pseudobulbar signs may appear in the preterminal phase; death usually ensues at some time between the ages of 30 and 60. Mo- lecular genetic diagnosis ispossible even in the presymptomatic phase, and treatment with bile acids (cheno- deoxycholic acid) can mitigate the disease manifestations and delay their progression (93, 658). Other lipidoses. Farb er’s lipogranulo- matosis and Wolman’s disease both cause death a few months after birth. Patients with neuronal ceroid lipofus- cinosis (Batten-Kufs disease) often die in infancy or early childhood (sub- forms known, respectively, as Haltia- Santavuori disease and Jansky- Bielschowsky disease), but some sur- vive into adolescence (Spielmeyer- Vogt disease) or even adulthood (Kufs disease) (94, 168). Ataxia, myoclonus, and intractable epilepsy are charac- teristic. Adolescents suffer progres- sive loss of vision. Patients with the adult form of the disease do not be- come blind, but do suffer from pro- gressive dementia (243). Leukodystrophies The leukodystrophiesaredisorde rs of myelin metabolism. Metachromatic leukodystrophy. In this autosomal recessive disease, a deficiency of arylsulfatase A leads to an accumulation of sulfatide in the brain, peripheral nerve tissue, and other tissues,including the kidneys. The disease usually becomes mani- fest in late inf ancy. Spasticity appears first, typically in the second year of life, followed by deterioration of mental function, disappearance of the 290 2DiseasesMainlyAffecting the Brain and its Coverings Mumenthaler, Neurology © 2004 Thieme All rights reserved. Usage subject to terms and conditions of license. intrinsic muscle reflexes, and devel- opment of bulbar andpseudobulbar signs, including dysarthria. Optic at- rophy and blindnessensue,and,fi- nally, quadriplegia and a persistent vegetative stat e. The juvenile form ap- pears between the 3rd and 10th years of life and is usually associated with a gait disorder, sometimes also with emotional disturbances and demen- tia (864). The adult form becomes manifest around age 30 with psychi- atric abnormalities or dementia, spasticity, and ataxia. T2-weighted MR images reveal confluent hyperin- tensity of the cerebral and cerebellar white matter. The cortex isatrophic (566) and the ventricles are dilated. The subcortical U-fibers are spared at first, but are later involved as the dis- ease progresses. Biochemical analysis of leukocytes and o f urine reveals the deficiency of arylsulfatase A. The pro- gression of the disease may be slowed or halted by bone marrow transplantation (543, 864). Krabbe ’s globoid cell leuko dystrophy (488). Galactocerebrosidase is the missing enzyme in this disease, whose most prominent signs are spasticity, optic atroph y, anddimin- ished nerve conduction velocity. When the disease arises in infancy,it is fatal in the first 2years of life. Child- hood and adult forms have also been described, with clinical features re- sembling those of metachromatic leukodystrophy (976). Mucopolysaccharidoses (859) The abnormalities of facial appear- ance that are specific to this group of diseases have been termed “gargoyl- ism” (see under Hurler’s disease, be- low). Each of these conditions is due to a deficiency of a specific enzyme (hydrolase), resulting in accumula- tion of acid mucopolysaccharides in the tissues. Hurler’s disease. This classic and most severe type of mucopolysaccha- ridosis beginsininfancyand usually leads to d eath by age 10. A lumbar gibbus deformity and corneal opacity are already evident in the first year of life. The joints become stiff and swol- len, the chest deformed; the hands and feet remain small and chubby, and stunted growth and mentalretar- dation are evident by age 2 or 3 years. The facial features are coar se, typified by a projecting forehead, bushy eye- brows, saddle nose, hypertelorism, and a lumpy tongue. The meninges may be thickened, and there may be hydrocephalus or spinalcordcom- pression leading to quadriparesis. Cardiac involvement is not infre- quently the cause of death. Scheie’s disease is a variant of Hurler’s disease with onset in childhood. Other mucopolysaccharidoses. These include Hunter’s, Sanfilippo’s, Mor- quio’s,andMaroteaux-Lamy diseases. Hunter’s disease is X-linked recessive. Sanfilippo’s disease mainly affects the brain, while the two last-named dis- eases mainly affect the skeleton. Mucolipidoses (859) These diseases, clinically similar to the mucopolysaccharidoses, ar e diag- nosed by the finding of elevated oli- gosa ccharide and glycopeptide levels in the urine. The sialidoses are a sub- class. Cerebral Metabolic Disorders 291 Mumenthaler, Neurology © 2004 Thieme All rights reserved. Usage subject to terms and conditions of license. Disorders of Amino Acid and Uric Acid Me tabolism Phenylketonuria. Phenylalanine hy- droxylase deficiency, though rare, is the m ost common disorder of amino acid and protein me tabolism. It is transmitted in an autosomal reces- sive inheritance pattern. In untreated children, failure of hydroxylation of phenylalanine to tyrosine impairs ce- rebral myelination and causes mental retardation and epilepsy. S pasticity and (often) tremor appear as the dis- ease progresses. The affected children are often blond and blue-eyed, be- cause tyrosineisaprecursor of mela- nin. The clinical neurologic findings are nonspecific. T2-weighted MRI re- veals hyperintensity of the white matter (747). Since the 1960s, all newborns have undergone diagnostic screening for this disorder by mea- surement of the serum phenylalanine concentration. A phenylalanine- restricted diet enables phenylketo- nurics to undergo normal motor and mental development(682). Maple syrup urine disease. This disor- der is an autosomal recessive enzyme deficiency leading to impaired me- tabolism of the branched-chain amino acids valine, leucine, and iso- leucine. Like phenylketonu ria, it is as- sociated with mental retardation. The urine has a characteristic sweet smell like that of maple syrup. The neurora- diologic findings are nonspecific (T2- hyperintensity of white matter) (138). Hartnup disease (286). This auto- somal recessive disorder is due to a defect in the intestinal and renal tu- bular transport of the neutral amino acids tryptophan, alanine, and histi- dine. Characteristic findings include a progressive, photosensitive, pellag ra- like dermatitis, ataxia, nystagmus, impaired gait, spasticity, and demen- tia. (Hartnup was the surname of the family in which the disease was origi- nally described.) Homocystinuria. This disorder of me- thionine metabolism leads to arterial and venous thromboembolism, ecto- pia lentis, and mental retardation. Heterozygous carriers are at in- creased risk for stroke and occlusive peripheral vascular disease. Reye’s syndrome. This disease is char- acterized by encephalopathy and fatty infiltration of the viscera. It is discussed further below (p. 296). Disorders of Carbohydrate Metabolism Glycogen storage diseases (235). Ta- ble 2.72 provides an overview of in- herited enzyme deficiencies that im- pair the metabolism of glucose and glycogen.Mostareinheritedinanau- tosomal rece ssive pattern; only type IX and the hepatic form of type VIII are X-linked recessive. Glucose-6- phosphatase deficiency and glycogen synthetase deficiency are character- ized by recurrent hypoglycemic cri- ses, presenting with somnolence, stu- por, or coma and generalized sei- zures, which may cause lasting neu- rologic damage (p. 898). The general- ized forms (types II, III, IV, and IX) cause intraneuronal glycogen storage, and thus mental retardation. Skeletal muscle involvement l eads to exercise intolerance, or to a myopathy resem- bling that of muscular dystrophy (p. 895). In type IX glycogen stora ge dis- ease, severe hemolytic anemia may be the major clinical finding. 292 2DiseasesMainlyAffecting the Brain and its Coverings Mumenthaler, Neurology © 2004 Thieme All rights reserved. Usage subject to terms and conditions of license. Table 2.72 Glycogen storage diseases Type Eponym Deficient enzyme Involved organs and tissues Clinical features Other remarks I von Gierke Glucose-6-phosphatase Liver, kidney Hypoglycemic crises, hepatomeg- aly II Pompe Acid maltase Generalized Cardiomegaly, weakness, hypoto- nia, death by 1 year Infantile form Acid maltase Generalized Muscular dystrophy, respiratory insufficiency Childhood form Acid maltase Generalized Proximal myopathy, respiratory insufficiency Adul t form III Cori, Forbes Debranching enzyme Generalized Hepatomegaly, hypoglycemia, progressive weakness IV Andersen Branching enzyme Generalized Hepatosplenomegaly, cirrhosis, hepatic failure V McArdle Myophosphorylase Skeletal muscle Exercise-induced weakness, myalgia, contractures, myoglobi- nuria VI Hers Hepatic phosphorylase Liver, skeletal muscle, erythrocytes Mild hypoglycemia, hepatomeg- aly VII Tarui Muscle phosphofructo- kinase Skeletal muscle, erythrocytes Exercise-induced weakness, myalgia, contractures, myoglobi- nuria Cont. Cerebral Metabolic Disorders 293 Mumenthaler, Neurology © 2004 Thieme All rights reserved. Usage subject to terms and conditions of license. Table 2.72 (Cont.) VIII Phosphorylase kinase Liver Asymptomatic hep atomegaly X-linked Phosphorylase kinase Liver,skeletalmuscle Hepatomegaly, short stature, hy- potonia Phosphorylase kinase Skeletal muscleExerciseintolerance, myoglobinu- ria Phosphorylase kinase Heart Lethal infantile cardiomyopathy IX Phosphoglycerate kinase Generalized Hemolytic anemia, mental retar- dation, exercise intolerance, myoglobinuria X-linked X Muscle phosphoglycer- ate mutase Skeletal muscle Exercise-induced weakness, myalgia, contractures, myoglobi- nuria XI Fanconi-Bickel Muscle lactate dehy- drogenase Skeletal muscle Exercise-induced weakness, myalgia, contractures, myoglobi- nuria Muscle lactate dehy- drogenase Liver Hypoglycemic crises, hepatomeg- aly 294 2DiseasesMainlyAffecting the Brain and its Coverings Mumenthaler, Neurology © 2004 Thieme All rights reserved. Usage subject to terms and conditions of license. Myoclonus epilepsy (497) (p. 512). Generalized epilepsy, myoclonus, and dementia are the characteristic fea- tures of thisautosomal r ecessi ve dis- ease. Its clinical signs include ataxia, spasticity, rigidity, and dysarthria. Thedisease usuall y appears in ado- lescence and then progresses inexo- rabl y to death in early adulthood. Au- topsy reveals intr aneuronal Lafora bodies containing polyglucosans. Polyglucosan body disease (Fig. 2.81). This is a further disease i n which polyglucosans accumulate. Patients generally pre sent in the fifth or sixth decade of life with spasticity, weak- ness due to involvement of the spinal anterior horn cells, sphincter distur- bances, sensory disturban ces, and, later, dementia (97d). This disease may be confused at f irst with amyo- trophic lateral sclerosis (p. 434). Disorders producing hypoglycemia. As discussed below, intermittent dis- turbances of carbohydrate metabo- lism lead to systemic hypoglycemia and its consequences for the brain (p. 113). Disorder s of glucose transport from the plasma across the blood- brain barrier into the neurons are much rarer . They are chara cteriz ed by intractable epileptic seizures that first appear in early childhood and take different forms depending on the age of the patient (229a). Cogni- tive and motor development are slowed. Low CSF concentratio ns of glucose and lactateareessentialto the diagnosis. Treatment A ketogenic diet can control the sei- zures, but unfortunately does not improve cognitive and motor de- velopment. Disorders of Glycosylation Carbohydrate-deficient glycoprotein syndrome (CDG syndrome) comprises agroupofmultisystemic disorders due to congenital defects of protein glycosylation, resulting in the forma- tion of functionally deficent glycopro - teins. The most common type is phos- phomannomutase deficiency (CDG- Ia), an autosomal recessive disorder characteriz ed initially by poor feeding and failure to thrive, a nd later by pys- chomotor retardation, pronounced axial hypotonia, muscle weakness, and cerebellar ataxia. Seizures may also occur, and abnormalities of the glycoproteins involved in hemostasis may cause both hemorrhagic and is- chemic strokes and cerebral veous thrombosis. Neuropathological exam- ination reveals olivopontocerebellar atrophy. Patients surviving into ado- lescence and adulthood sometimes achieve some degree of social fun- tioning, but not independence. Diseases Whose Pathogenesis is Incompletely Understood Alexander disease (124). This illness appears in early childhood and is characterized by macrocephaly, spas- ticity, seizures, and dementia, pro- gressing within a few years to a vege- tative state and death. It rarely arises in adulthood, in which case it pre- sents with dementia. The histological findings include Rosenthal fibers and diffuse demyelination. Schilder’s diffuse cerebral sclerosis (encephalitis periaxialis diffusa). This is a progressive leukoencephalopathy manifesting as progressive dementia, psychosis, corticospinal signs, and blindness, which may be the result either of optic neuritis or of cor- Cerebral Metabolic Disorders 295 Mumenthaler, Neurology © 2004 Thieme All rights reserved. Usage subject to terms and conditions of license. tical lesions. It is considered a variant of multiple sclerosis (p. 484 ff.) (766) and its cause is unknown. Pelizaeus-Merzbacher disease (chronic infantile cerebral sclerosis). This disease, one ofthesudanophilic leukodystrophies, is inherited in an autosomal recessive pattern and pre- sents in the first few months or years of life. Its major features are tremor, cerebellar ataxia, n ystagmus, and, later, paraparesis and dementia. MRI shows T2-hyperintensity of the white matter (878). Adrenoleukodystrophy (679). This X- linked recessive heritable disorder is due to a deficiency of lignoceroyl CoA synthetase,anenzymethatisneces- sary for the beta-oxidation of long- chain fatty acids. Boys are affected in the first or second decade of life, at first with mental changes, gait distur- bance, visual impairment, and d ysar- thria, and later with progressive quadriparesis. In adult patients, adre- nal insufficiency rather than spasti- city may dominate the clinical pic- ture. Adrenomyeloneuropathy is a form of the disorder in which there is also a polyneuropathy. A diagnostic finding is an elevation of the serum concentration of very-long-chain fatty acids. The progression of neuro- logic impairment may be slowed by a diet low in fatty acids and by bone marrow transplantation. The hope of therapeutic benefit from “Lorenzo’s oil,” which inspired a popular film of the same name, has, unfortunately, not been fulfilled (679). Canavan’s dis ease. This autosomal re- cessive disorder becomes clinically apparent in the first few months of life. A deficiency of enoyl CoA hydra- tase impairs myelination and thus causes developmental delay with blindness, hypotonia, spasticity, and macrocephaly. Reye’s syndrome. In 1963, Reye et al. described a childhood encephalopathy with fatty infiltration of the viscera (784). The syndrome is probably me- diated by mitochondrial dysfunction of multifactorial cause (967). It ap- pears a few days after a viral infection and consists of persistent vomiting, somnolence, delirium, and coma. There is a statistically significant asso- ciation with the use of aspirin. The CSF is normal. Imaging studies show cerebral edema, and the EEG reveals evidence of encephalopathy (slowing and triphasic waves). There is no spe- cific diagnostic test. In the first few years after its original description, Reye’s syndrome wasusuallyfatal; with current intensive-care methods, its mortality has been reduced to 30%. Leigh syndrome. This neurodegenera- tive disease was described in 1951 (569). It may already be manifest as lactic acidosis in the neonate, or it may appear later with ataxia, flaccid weakness, hypo reflexia, ophthalmo- plegia, optic atrophy, and delayed growth and development. MRI reveals symmetrical lesions resembling in- farcts in the bas al ganglia, thalamus, and brainstem. The serum and CSF concentrations of pyruvate and lac- tate are elevated (825). Point muta- tions of mitochondrial DNA have been found in a few patients; thus, at least some patients with Leigh syndrome suffer from a mitochondrial encepha- lomyopathy (p. 899) (235, 825). Alipoproteinemias Lipoproteins are needed for lipid transport in the blood. Abetalipopro- 296 2DiseasesMainlyAffecting the Brain and its Coverings Mumenthaler, Neurology © 2004 Thieme All rights reserved. Usage subject to terms and conditions of license. [...]... or lung cancer Anti-Hu = ANNA-1 Encephalomyelitis, limbic encephalitis, opsoclonusmyoclonus syndrome (41 5), sensory polyneuropathy Small-cell lung cancer, neuroblastoma, prostate cancer, seminoma Anti-Ri = ANNA-2 Opsoclonus-myoclonus syndrome Neuroblastoma, breast cancer, small-cell lung cancer Anti-Retina Paraneoplastic retinopathy Small-cell lung cancer Anti-NMJ Lambert-Eaton myasthenic syndrome (Ab... syndrome Mumenthaler, Neurology © 20 04 Thieme All rights reserved Usage subject to terms and conditions of license 322 Table 2.87 575, 768) 2 Diseases Mainly Affecting the Brain and its Coverings Autoantibodies associated with paraneoplastic neurologic syndromes (207, Antibody Syndrome Tumor Anti-Yo = PCA-1 Cerebellar degeneration Ovarian carcinoma, breast cancer, (rarely) lymphoma or lung cancer Anti-Hu... Pseudosclerosis) (669, 719, 834a, 902) Pathogenesis The prevalence of this autosomalrecessive disorder of copper metabo- 297 lism is ca one in 30,000, corresponding to a frequency of the causative allele of ca one in 14 0-2 00 The affected gene, on chromosome 13q 14. 3, encodes a copper-transporting ATPase The defect causes an abnormally low plasma concentration of the copper-transport protein ceruloplasmin,... Medication-Induced Extrapyramidal Disorders (337) Medications may be the cause of several different kinds of extrapyramidal disorder (Table 2.78) Acute dystonia and dyskinesia Neuroleptics such as phenothiazines, Mumenthaler, Neurology © 20 04 Thieme All rights reserved Usage subject to terms and conditions of license 306 2 Diseases Mainly Affecting the Brain and its Coverings Table 2.78 Medication-induced... disorder, or even iatrogenic pseudo-Gilles de la Tourette syndrome (519, 901; cf p 272) Pisa syndrome, involving lateral inclination and torsion of the trunk, neck, and head, is most commonly seen in Mumenthaler, Neurology © 20 04 Thieme All rights reserved Usage subject to terms and conditions of license Systemic Diseases elderly patients after chronic neuroleptic use ( 548 ) (The odd, and perhaps inappropriate,... (marijuana) Hallucinogens: > LSD > “Ecstasy” (= 3,4methylenedioxymethamphetamine, MDMA) > Psilocybin Inhaled (“sniffed”) substances: Solvents, gasoline; glue or paint containing toluene, n-hexane, aliphatic hydrocarbons, nitrous oxide, trichloroethylene, etc Phencyclidine (“angel dust”) Anticholinergics Ethanol Tobacco Mumenthaler, Neurology © 20 04 Thieme All rights reserved Usage subject to terms... neuropathies and plexopathies often result from the lack of shifting movements during drug-induced stupor and coma, in distinction to normal sleep (e.g., the well-known “Saturday night palsy” of the radial nerve) Finally, MPTP (p 245 ) causes parkinsonism, and the smoking of heroin pyrolysate causes leukoencephalopathy (44 4) Treatment Acute opioid or benzodiazepine intoxication can be treated with the respective... complicating conditions (see above discussion) Such conditions, if already present, will require specific treatment Mumenthaler, Neurology © 20 04 Thieme All rights reserved Usage subject to terms and conditions of license Systemic Diseases 313 Endocrine Disorders with Neurologic Manifestations Overview: Endocrine disorders cause metabolic derangements that, in turn, give rise to metabolic encephalopathy, which... drugs of abuse: > Alcohol > Beta-blockers > Salicylates Hyperinsulinism: > Insulinoma Exogenous insulin > Sulfonylurea > Accelerated glucose metabolism: > Extrapancreatic tumors > Systemic carnitine deficiency > Lipid oxidation disorders > Cachexia with fat depletion Mumenthaler, Neurology © 20 04 Thieme All rights reserved Usage subject to terms and conditions of license 3 14 Table 2.83 2 Diseases Mainly... folds with mucopolysaccharides), and facial pain > Myopathy (p 9 14) (830, 929, 975, 1029) is common in hypothyroidism, typically presenting with myalgia and a feeling of stiffness Some 30 40 % of patients develop myopathic weakness, which usually involves the pelvic muscles and the proximal muscles of the lower Mumenthaler, Neurology © 20 04 Thieme All rights reserved Usage subject to terms and conditions . in 14 0-2 00. The af- fected gene, on chromosome 13q 14. 3, encodes a copper-transporting ATPase. The defect causes an abnor- mally low plasma concentration of the copper-transport protein cerulo- plasmin,. diag- nosed by the finding of elevated oli- gosa ccharide and glycopeptide levels in the urine. The sialidoses are a sub- class. Cerebral Metabolic Disorders 291 Mumenthaler, Neurology © 20 04 Thieme All. cases, hypointense on T 1- or T2-weighted MR images. Basal ganglionic calcifica- tion is an exception to the latter rule: it tends tobehyperintenseonT 1- weigh ted images, and hypo- or hyper- intense on T2-weighted