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Lafora's disease: What is the best site for skin biopsy?
Brief communications Lafora's disease: What is the best site for skin biopsy? Curt P. Samlaska, MAJ, MC, USA,a John McBurney, MAJ, MC, USA,b Purnima Sau, COL, MC, USA,a and William D. James, LTC, MC, USAa Washington, D.C.
Lafora's disease is an autosomal recessive inherited form of progressive epilepsy characterized by seizures, myoclonus, and dementia. Diagnosis is established on demonstration of characteristic cytoplasmic inclusions, called Lafora bodies, in the brain, striated muscle liver or skin. Despite the absenceof cutaneousfinding;, typi~ cal periodic acid-Schiff (PAS)-positive inclusions in skin biopsy specimens are present in eccrine ducts, axillary apocrine myoepithelial cells, and peripheral nerves. Including the case reportedhere, there are eight patients with Lafora's disease confirmed byaxillary biopsies. The axilla shouldbe the site of choicefor random cutaneous biopsytoexcludeLafora's disease becauseof the presence of both eccrineand apocrine structures. Lafora's diseasewas first described by Unverricht! in 1891. The main clinicalmanifestations are seizures, myoclonus, and dementia,with onsetoccurring between the ages of 10 and 19 years.?The initial manifestations are decreased scholastic performance, behavioral disorders, or generalized convulsions.s" Myoclonic jerks associated with progressive dementia develop within the next few years.2-4 Death occurswithin 2 to 10 years as a result of heart failure, liver failure, or aspiration pneumonia.l? The disease is transmitted by an autosomalrecessive pattern of inheritance and is frequently associated with parental consanguinity.' The diagnosis is confirmed on demonstration of characteristicLafora bodies at autopsy(in brain, heart, choroidplexus, spinalnerves, andstriated muscle)or in biopsy specimens of brain, muscle, liver, or skin. 2-4 Carpenter and Karpati'' were the first to note PAS-positive inclusionsineccrinesweatducts.Subsequentcasereportshave confirmed the importance of random skin biopsies to confirmthe diagnosis of Lafora's disease.s4-? Skinbiopsy specimens havebeen obtainedfrom the calf,S, 6 forearm," back,' and recently the axilla. 5, 8 Grahmann et a1. 9 recently described a patient with Lafora's disease in whom Lafora bodies could not be found in the skin. From the Dermatology Service" and Department of Neurology, b Walter Reed Army Medical Center. The opinions or assertions containedhereinare the privateviews of the authors and are not to beconstruedas official or asreflecting the views of the Department of the Army or the Department of the Defense. Reprints not available.
Fig. 1. Photomicrograph of PAS-positive cytoplasmic inclusions in apocrineglands. (XIOO.) Case report. A 21-year-old woman was admitted for evaluation of myoclonic seizures. At the age of 14 years she had her first seizure. She was an "A" student until her sophomore year in college, when she had another generalized seizure. Her academic standing rapidly declined. There was no family history of consanguinity. Neurologic examination was most remarkable for severe dementia and frequent small-amplitude myoclonic jerks. Examination of the skin was noncontributory. An electroencephalogram revealed generalized, high-voltage, irregular decreases in frequency and frequent high-voltage independent spikes, polyspikes, and spike-wave complexes. An electroretinogram was normal. A computerized axial tomogram and a magnetic resonance spectrogram ofthe head were normal.
Histopathologic findings. Two punch biopsyspecimens were taken from the left axilla. The hematoxylin-andeosin-stained sections revealed normal apocrine and eccrinesweat glands and ducts. Sections stained with PAS demonstratednumerousstrongly PAS-positive, diastaseresistant,roundto ovalinclusionbodiesin the basal areas ofapocrinesweatglands(Fig. 1). These bodieswerenoted also in the eccrine and apocrine sweat ducts. Under electron microscopy the inclusions were round to oval, intracytoplasmic, electron-lucent areas adjacent tothe nucleusofboth the apocrine myoepithelialcells and eccrineand apocrinesweat duct cells. A strikingpredominance of the inclusions was noted in the myoepithelial cells in the basal areas of apocrine glands (Fig. 2). Discussion. There are two forms of Lafora's disease. The classicor Unverrichtvariety beginsbeforethe age of 15 years, and death usually occurs before the age of 25 years. Our patient is an example of this type. The more protracted or Lundborg variety begins between the ages of 16and 20 years,and death usuallyoccurs after the age of 40 years." Lafora's diseaseis considered to be a metabolicdisorder caused by the characteristic inclusionsand by an au-
791
792
Journal of the American Academy of Dermatology
Brief communications
Busard et al.5, 8 have performed axillary biopsies on tissue from seven patients with Lafora's disease and from their immediate families. All patients demonstrated characteristic inclusions in eccrine duct epithelium. Our findings are in agreement with those of Busard et al. 5,8 In conclusion, axillary skin biopsy is an easy, relia ble diagnostic tool for patients with clinical signs of Lafora's disease. REFERENCES
Fig. 2. Electron micrograph demonstrates filamentous
and fine granular matrix within non-membrane-bound inclusion body (I) within myoepithelial cell. Inclusion bodies are located away from basal lamina (BL). (X23,700.) tosomal recessive inheritance pattern. A specific enzyme defect has not been detected." The inclusions consist of glucose polymers (polyglucosans), with variable amounts of phosphate and sulfate groups and less than 5% associated proteins.!" Ultrastructurally, Lafora bodies lack a limiting membrane except in striated muscle. I I, 12 In the proper clinical setting, the presence of Lafora bodies will confirm the diagnosis. The detection of Lafora bodies by themselves, however, is not diagnostic. Similar polyglucosan inclusions can be seen in the course of normal aging (amyloid bodies); double athetosis syndrome; amyotrophic lateral sclerosis, and glycogen storage disease, type IV; and in a group of patients with progressive lower and upper motor neuron deficits, marked sensory loss of the lower extremities, neurogenic bladder, and dementia." 10 Cutaneous manifestations of Lafora's disease are rare. Papulonodular lesions on the inner aspect of the ears and indurated thickened plaques on the forearms have been observed.' In another case a patient had erythematous, puffy, indurated earlobes with dilation and plugging of the follicular orifices.l-? Eccrine glands appear in the highest concentrations in the palms, soles, and axilla. On the basis of this finding,
1. Unverricht H. Die Myoclonic. Leipzig: Franz Deuticke, 1891:1-128. 2. Newton GA, Sanchez RL, Sweda J, et a!. Lafora's disease: the role of skin biopsy. Arch Dermatol 1987;123:1667-9. 3. Van Heycop Ten Ham MW. Lafora disease: a form of progressivemyoclonus epilepsy. In: Vinken PJ, Bruyn GW, eds. Handbook of clinical neurology. New York: North Holland,1974;27:171-89. 4. BerkovicSF, Andermann F, Carpenter S, et aI. Progressive myoclonus epilepsies: specificcauses and diagnosis. N Engl J Med 1986;315:296-303. 5. Busard BL, Renier WO, Gabreels PJM, et al, Lafora's disease: comparison of inclusion bodies in skin and in brain. Arch NeuroI1986;43:296-9. 6. Carpenter S, Karpati G. Sweat gland duct cells in Lafora disease: diagnosis by skin biopsy. Neurology 1981;3 I: 1564-8. 7. White JW, Gomez MR:Diagnosis of Lafora disease by skin biopsy. J Cutan PathoI1988;15:171-5. 8. Busard HL, Gabreels-Festen AA, Renier WO, et al. Axilla skin biopsy: a reliable test for the diagnosis of Lafora's disease. Ann Neural 1987;21:599-601. 9. Grahmann FC, Janzer RC, Hecker A, et aI. Progressive myoclonic epilepsy (Unverricht type) with atypical Lafora bodies: case report. Eur Arch Psychiatry Neurol Sci 1986;235:259-62. 10. Robitaille Y, CarpenterS, Karpati G, eta!. A distinct form of adult polyglucosan body disease with massive involvement of central and peripheral neuronal processes and astrocytes: a report of four cases and a review of the occurrence of polyglucosan bodies in other conditions such as Lafora's disease and normal ageing. Brain 1980;103:31536. 1L Carpenter S, Karpati G, Andermann F, et a!. Lafora's disease: peroxisomal storage in skeletal muscle. Neurology 1974;24:531-8. 12. Neville HE, Brooke MH, Austin JR. Studies in myoclonus epilepsy (La fora body form). IV. Skeletal muscle abnormalities. Arch NeuroI1974;30:446-74.
Development of nail pigmentation during zidovudine therapy Kenya H. Anders, MD, and Donald C. Abele, MD
Augusta, Georgia Zidovudine (Retrovir, AZT) administration has been associated with progressive pigmentary changes in the From the Department of Dermatology, Medical College of Georgia. Reprint requests: Donald C. Abele, MD, Department of Dermatology, 1521 Pope Ave., Augusta, GA 30912-2900.
16/4/13557
Lafora's disease is an autosomal recessive inherited form of progressive epilepsy characterized by seizures, myoclonus, and dementia. Diagnosis is established on demonstration of characteristic cytoplasmic inclusions, called Lafora bodies, in the brain, striated muscle liver or skin. Despite the absenceof cutaneousfinding;, typi~ cal periodic acid-Schiff (PAS)-positive inclusions in skin biopsy specimens are present in eccrine ducts, axillary apocrine myoepithelial cells, and peripheral nerves. Including the case reportedhere, there are eight patients with Lafora's disease confirmed byaxillary biopsies. The axilla shouldbe the site of choicefor random cutaneous biopsytoexcludeLafora's disease becauseof the presence of both eccrineand apocrine structures. Lafora's diseasewas first described by Unverricht! in 1891. The main clinicalmanifestations are seizures, myoclonus, and dementia,with onsetoccurring between the ages of 10 and 19 years.?The initial manifestations are decreased scholastic performance, behavioral disorders, or generalized convulsions.s" Myoclonic jerks associated with progressive dementia develop within the next few years.2-4 Death occurswithin 2 to 10 years as a result of heart failure, liver failure, or aspiration pneumonia.l? The disease is transmitted by an autosomalrecessive pattern of inheritance and is frequently associated with parental consanguinity.' The diagnosis is confirmed on demonstration of characteristicLafora bodies at autopsy(in brain, heart, choroidplexus, spinalnerves, andstriated muscle)or in biopsy specimens of brain, muscle, liver, or skin. 2-4 Carpenter and Karpati'' were the first to note PAS-positive inclusionsineccrinesweatducts.Subsequentcasereportshave confirmed the importance of random skin biopsies to confirmthe diagnosis of Lafora's disease.s4-? Skinbiopsy specimens havebeen obtainedfrom the calf,S, 6 forearm," back,' and recently the axilla. 5, 8 Grahmann et a1. 9 recently described a patient with Lafora's disease in whom Lafora bodies could not be found in the skin. From the Dermatology Service" and Department of Neurology, b Walter Reed Army Medical Center. The opinions or assertions containedhereinare the privateviews of the authors and are not to beconstruedas official or asreflecting the views of the Department of the Army or the Department of the Defense. Reprints not available.
Fig. 1. Photomicrograph of PAS-positive cytoplasmic inclusions in apocrineglands. (XIOO.) Case report. A 21-year-old woman was admitted for evaluation of myoclonic seizures. At the age of 14 years she had her first seizure. She was an "A" student until her sophomore year in college, when she had another generalized seizure. Her academic standing rapidly declined. There was no family history of consanguinity. Neurologic examination was most remarkable for severe dementia and frequent small-amplitude myoclonic jerks. Examination of the skin was noncontributory. An electroencephalogram revealed generalized, high-voltage, irregular decreases in frequency and frequent high-voltage independent spikes, polyspikes, and spike-wave complexes. An electroretinogram was normal. A computerized axial tomogram and a magnetic resonance spectrogram ofthe head were normal.
Histopathologic findings. Two punch biopsyspecimens were taken from the left axilla. The hematoxylin-andeosin-stained sections revealed normal apocrine and eccrinesweat glands and ducts. Sections stained with PAS demonstratednumerousstrongly PAS-positive, diastaseresistant,roundto ovalinclusionbodiesin the basal areas ofapocrinesweatglands(Fig. 1). These bodieswerenoted also in the eccrine and apocrine sweat ducts. Under electron microscopy the inclusions were round to oval, intracytoplasmic, electron-lucent areas adjacent tothe nucleusofboth the apocrine myoepithelialcells and eccrineand apocrinesweat duct cells. A strikingpredominance of the inclusions was noted in the myoepithelial cells in the basal areas of apocrine glands (Fig. 2). Discussion. There are two forms of Lafora's disease. The classicor Unverrichtvariety beginsbeforethe age of 15 years, and death usually occurs before the age of 25 years. Our patient is an example of this type. The more protracted or Lundborg variety begins between the ages of 16and 20 years,and death usuallyoccurs after the age of 40 years." Lafora's diseaseis considered to be a metabolicdisorder caused by the characteristic inclusionsand by an au-
791
792
Journal of the American Academy of Dermatology
Brief communications
Busard et al.5, 8 have performed axillary biopsies on tissue from seven patients with Lafora's disease and from their immediate families. All patients demonstrated characteristic inclusions in eccrine duct epithelium. Our findings are in agreement with those of Busard et al. 5,8 In conclusion, axillary skin biopsy is an easy, relia ble diagnostic tool for patients with clinical signs of Lafora's disease. REFERENCES
Fig. 2. Electron micrograph demonstrates filamentous
and fine granular matrix within non-membrane-bound inclusion body (I) within myoepithelial cell. Inclusion bodies are located away from basal lamina (BL). (X23,700.) tosomal recessive inheritance pattern. A specific enzyme defect has not been detected." The inclusions consist of glucose polymers (polyglucosans), with variable amounts of phosphate and sulfate groups and less than 5% associated proteins.!" Ultrastructurally, Lafora bodies lack a limiting membrane except in striated muscle. I I, 12 In the proper clinical setting, the presence of Lafora bodies will confirm the diagnosis. The detection of Lafora bodies by themselves, however, is not diagnostic. Similar polyglucosan inclusions can be seen in the course of normal aging (amyloid bodies); double athetosis syndrome; amyotrophic lateral sclerosis, and glycogen storage disease, type IV; and in a group of patients with progressive lower and upper motor neuron deficits, marked sensory loss of the lower extremities, neurogenic bladder, and dementia." 10 Cutaneous manifestations of Lafora's disease are rare. Papulonodular lesions on the inner aspect of the ears and indurated thickened plaques on the forearms have been observed.' In another case a patient had erythematous, puffy, indurated earlobes with dilation and plugging of the follicular orifices.l-? Eccrine glands appear in the highest concentrations in the palms, soles, and axilla. On the basis of this finding,
1. Unverricht H. Die Myoclonic. Leipzig: Franz Deuticke, 1891:1-128. 2. Newton GA, Sanchez RL, Sweda J, et a!. Lafora's disease: the role of skin biopsy. Arch Dermatol 1987;123:1667-9. 3. Van Heycop Ten Ham MW. Lafora disease: a form of progressivemyoclonus epilepsy. In: Vinken PJ, Bruyn GW, eds. Handbook of clinical neurology. New York: North Holland,1974;27:171-89. 4. BerkovicSF, Andermann F, Carpenter S, et aI. Progressive myoclonus epilepsies: specificcauses and diagnosis. N Engl J Med 1986;315:296-303. 5. Busard BL, Renier WO, Gabreels PJM, et al, Lafora's disease: comparison of inclusion bodies in skin and in brain. Arch NeuroI1986;43:296-9. 6. Carpenter S, Karpati G. Sweat gland duct cells in Lafora disease: diagnosis by skin biopsy. Neurology 1981;3 I: 1564-8. 7. White JW, Gomez MR:Diagnosis of Lafora disease by skin biopsy. J Cutan PathoI1988;15:171-5. 8. Busard HL, Gabreels-Festen AA, Renier WO, et al. Axilla skin biopsy: a reliable test for the diagnosis of Lafora's disease. Ann Neural 1987;21:599-601. 9. Grahmann FC, Janzer RC, Hecker A, et aI. Progressive myoclonic epilepsy (Unverricht type) with atypical Lafora bodies: case report. Eur Arch Psychiatry Neurol Sci 1986;235:259-62. 10. Robitaille Y, CarpenterS, Karpati G, eta!. A distinct form of adult polyglucosan body disease with massive involvement of central and peripheral neuronal processes and astrocytes: a report of four cases and a review of the occurrence of polyglucosan bodies in other conditions such as Lafora's disease and normal ageing. Brain 1980;103:31536. 1L Carpenter S, Karpati G, Andermann F, et a!. Lafora's disease: peroxisomal storage in skeletal muscle. Neurology 1974;24:531-8. 12. Neville HE, Brooke MH, Austin JR. Studies in myoclonus epilepsy (La fora body form). IV. Skeletal muscle abnormalities. Arch NeuroI1974;30:446-74.
Development of nail pigmentation during zidovudine therapy Kenya H. Anders, MD, and Donald C. Abele, MD
Augusta, Georgia Zidovudine (Retrovir, AZT) administration has been associated with progressive pigmentary changes in the From the Department of Dermatology, Medical College of Georgia. Reprint requests: Donald C. Abele, MD, Department of Dermatology, 1521 Pope Ave., Augusta, GA 30912-2900.
16/4/13557