Inherited multiple meningiomas: a clinical, pathological and cytogenetic study of an affected family.

The clinical features of a family with inherited multiple meningiomas as the major manifestation of neurofibromatosis are presented. The value of noninvasive radiological screening investigations is emphasised. The results of cytogenetic and pathological studies on the family are presented and discussed with a review of the relevant literature.     

Semantic dementia: clinical, radiological and pathological perspectives

Semantic dementia (SD) is a recently described clinical syndrome characterised by an acquired progressive inability to name or comprehend common concepts, with little or no distortion of the phonological and syntactic aspects of language, and relative sparing of other aspects of cognition, such as episodic memory, nonverbal problem-solving, and perceptual and visuo-spatial skills. The cognitive locus of this syndrome appears to lie in the permanent store of long-term memory representing general world knowledge-semantic memory. The anatomical distribution of atrophy is less well-defined, and the contribution of various imaging modalities is discussed in the context of a body of 45 published and unpublished cases. We conclude that involvement of the left infero-lateral temporal cortex is the critical area in the genesis of SD. SD probably always represents a non-Alzheimer neurodegenerative process; a variety of pathological lesions may be present, and possible causes, together with debates about their correct classification, are discussed. Received: 1 March 1999, Received in revised form: 20 November 1999, Accepted: 29 November 1999     

Dentatorubropallidoluysian atrophy in a spanish family: a clinical, radiological, pathological, and genetic study

The object was to describe the clinical, radiological, pathological, and genetic findings in a Spanish family with dentatorubropallidoluysian atrophy (DRPLA). This is an inherited neurodegenerative disease, well recognised in Japan, but with few cases reported from Europe and America and no cases published from Spain. The clinical misdiagnosis of Huntington's disease is not infrequent. Pedigree analysis and clinical data of a family were collected. A genetic study was performed in two patients. Pathological information was obtained from the necropsy of one patient. RESULTS: Pedigree analysis showed an autosomal dominant pattern of inheritance. Age at onset varied from 5 to 55 years. Ataxia and chorea were present in most of the members. Some of these had a long course disease with late dementia. Four patients had seizures and early mental impairment. In one patient, cranial MRI showed cortical, brain stem and cerebellar atrophy, and white matter changes. In another patient, necropsy showed atrophy of the globus pallidus and lipofuscin deposits in dentate and pallidal neuronal cells. Genetic study showed an abnormal CAG triplet expansion in the B37 gene on chromosome 12. As in other cases previously reported, Spanish cases of DRPLA show intrafamilial phenotypic heterogeneity. Clinical and MRI data could differentiate DRPLA from Huntington's disease but definitive diagnosis requires molecular studies. Pathological studies are still necessary to correlate DRPLA brain involvement with the clinical and molecular findings.     

Neuroacanthocytosis: clinical,radiological, and neurophysiological findings in an Italian family

Abstract. We have studied three members of a family (mother and two siblings) where the mother and father were first cousins and who presented a history of progressive mental deterioration, hyperkinetic extrapyramidal disorders, and epileptic seizures. They underwent the following examinations: cupremia, cupruria, and level of ceruloplasmin, genetic analysis for SCA1, 2, 3, 6, dentato-rubric-pallido-luysian atrophy, and Huntingtons disease, electromyography (EMG), electroencephalography (EEG), brain magnetic resonance imaging (MRI), and investigation of acanthocytes with scanning electron microscopy. Genetic analysis was negative in all patients and acanthocytes were positive. EMG showed an axonal neuropathy in one sibling, EEG showed epileptiform activity in the two siblings, and MRI showed cortical atrophy in all subjects. This family shows the great variability of neuroacanthocytosis and a dominant autosomal transmission, as described only once previously in the literature.     

Methylmercury poisoning, Clinical follow-up and sensory nerve conduction studies.

Methylmercury poisoning occurred in four cases after passage of methylmercury through the food chain. The neurological damage in all four cases was severe. The damage was greater at younger ages with maximum involvement in the case of transplacental poisoning. Significant recovery occurred in two cases, but on six-year follow-up two cases remained severely impaired. Clinical and electrophysiological evidence suggests that damage to peripheral sensory nerves may not be the cause of the late sensory symptomatology.     

Joseph's disease: clinical and pathological studies in a Japanese family

Joseph's disease is a hereditary ataxia found among descendants of Portuguese from the Azores Islands. We describe the clinical and pathological features of 4 members of a Japanese family who were diagnosed as having Joseph's disease. The illness began with cerebellar ataxia between the ages of 18 and 45 years. Nystagmus, dysarthria, and pyramidal signs were early manifestations. External ophthalmoplegia, dystonia and/or athetotic movements, and muscular atrophy appeared in the late stages. Neuropathological findings in one patient revealed degeneration of the dentatorubral and pallidoluysian systems, substantia nigra, pontocerebellar system, Clarke's column and spinocerebellar tracts, and anterior horn cells, as well as the cranial nuclei in the brainstem. Neurons in the inferior olivary nuclei, Purkinje's and granule cells, the cerebral cortex, thalamus, and striatum were spared. Involvement of the dentatorubral and pallidoluysian systems seems to be a characteristic feature of this disease in Japan.     

Methanol poisoning: A clinical and pathological study

We report 2 survivors of severe methanol poisoning who developed, apart from blindness, a Parkinson-like extrapyramidal syndrome characterized by reduced initiative, poor voice volume, masked facies, mild tremor, rigidity, and bradykinesia. Both patients were mildly demented and 1 had hyperreflexia and bilateral Babinski responses. Computed tomographic scans in both patients demonstrated bilateral symmetrical infarction of the frontocentral white matter and putamen. Electromyography in 1 patient showed extensive denervation, mainly involving the legs, but normal motor conduction velocities. L -Dopa administered to the more severely affected patient had no effect on the parkinsonian features. Autopsy revealed cystic resorption of the putamen and the frontocentral subcortical white matter in addition to widespread neuronal damage throughout the cerebrum, cerebellum, brainstem, and spinal cord.     

Central neurocytoma: a clinical, radiological and pathological study of nine cases

PURPOSE: Central neurocytoma is a rare intraventricular brain tumor that affects young adults and presents with increased intracranial pressure secondary to obstructive hydrocephalus. Typically, it has a favorable prognosis after adequate surgical intervention, but in some cases the clinical course is more aggressive. In this report, we describe the diagnosis and treatment of central neurocytoma in a series of patients at our institution. PATIENTS AND METHODS: Our series of nine patients (M:F=2:7, mean age, 28.2 years) with ventricular tumors showed typical radiological, histologic and immunohistochemical features of central neurocytoma. Most patients received craniotomy with removal of the tumor through transcallosal or transcortical approach. The surgical and histopathologic data of these patients were reviewed and analyzed. RESULTS: The prognosis is generally favorable. Although most patients were alive and well at the last follow-up, two developed recurrence. Typical histologic features of recurrent neurocytoma include high proliferative activity (MIB-1 labeling index: 2.0-6.8%), prominent vascular proliferation and remarkable synaptophysin expression. Two patients (non-recurrent) died during follow-up due to sepsis or central failure. The MIB-1 labeling indices were as high as 2.2-5.4% for these two patients. CONCLUSION: Although central neurocytoma is generally a benign neoplasm, some variant forms of recurrence are also present. Complete resection provides favorable long-term prognosis in most cases. Recurrent tumors are often local and the patients seem to recover well after a second resection followed by radiotherapy. Histologic features such as tumor proliferation (MIB-1 labeling index), vascular proliferation, and synaptophysin expression are often prominent in the recurrent tumor. We recommend that these histologic features be considered for tumor recurrence during treatment and follow-up of these patients.     

The clinical and radiological profile of primary lateral sclerosis: an annotation on its pathological and clinical background

Journal of Neurology -     

Intracranial chordoid glioma: A clinical,radiological and pathological study of 14 cases

BackgroundChordoid gliomas (CGs) are rare neuroepithelial tumors, which commonly arise from the anterior part of the third ventricle. Most studies on CGs included only one or two cases. To better understand the disease, we report 14 patients with pathologically confirmed CGs.MethodThe clinical characteristics, including radiological and histological examination, operative records, and prognoses were analyzed and reviewed.ResultThe case series included six male and eight female patients with an average age of 44.4 years. The most common preoperative symptom was headache (64.3%) and visual deterioration (57.1%). Radiological results showed that the third ventricle (12/14) was the most common site of the brain involved, and the lesions presented with solid (n = 9, 64.3%) or cystic-solid (n = 5, 35.7%) appearance. All patients were misdiagnosed as non-CG tumors. The operation approach was mainly determined by tumor location, thus trans-callosal approach (9/14) and trans-laminar terminalis approach were commonly used. Gross total resection (GTR) was achieved in all cases and none of them received any adjuvant therapy postoperatively. The most frequent postoperative complications were diabetes insipidus, electrolyte disturbance, hypopituitarism, cognitive dysfunction, and obstructive hydrocephalus. During an average follow-up period of 40.1 months, 2 cases (14.3%) were died of refractory hypopituitarism and pulmonary embolism, respectively. The preoperative symptoms and postoperative complications were all significantly improved in other 12 patients, and MRI showed no tumor recurrence.ConclusionAccording to our experience, we recommend GTR as the primary goal, which is associated with improved rates of tumor control and without increasing rates of postoperative complications.     

Congenital arachnoid cyst with unusual clinical, radiological, and pathological findings

Choroid plexus-like structures were found in the wall of a congenital frontotemporal arachnoid cyst in a 14-year-old girl who presented with temporal lobe seizures since the age of 6. The temporal cortex beneath the cyst was maldeveloped. The clinical, radiological, and pathological aspects of congenital arachnoid cysts are reviewed.     

Primary central nervous system sarcomas in children: clinical,radiological, and pathological features

Patients and methods The clinical, radiological, surgical, and pathological findings of 16 children with a primary central nervous system (CNS) sarcoma are reported. There were 8 (50%) girls and 8 (50%) boys ranging in age from 4 months to 14 years (mean age 4.8 years). Four patients (23%) were in their 1st year of life. Fourteen children (87%) had an intracranial sarcoma, and 2 (13%) had intraspinal tumors. Nine intracranial tumors (60%) were supratentorial. The parietal and temporal regions were the most frequently involved sites.Results Characteristic imaging findings included tumor cysts in 7 patients and marked tumoral enhancement in 9 (69%) with intratumoral calcification and hemorrhage. All patients underwent at least one operation to surgically remove the tumor with the aim of maximal resection and 3 patients underwent a second resection due to a recurrent tumor. Resection was total in 9 (53%) patients and subtotal in another 7 (41%). Dural attachment by tumor was confirmed in 7 (44%) patients and parenchymal invasion was present in 9 (56%). In one-third of the patients there was a well-defined plane of dissection around the tumor. Postoperative radiation was used in 10 patients. Postoperative chemotherapy was used in all but 2 patients. Immunohistochemical studies were available in 13 patients with the most consistent finding being strong vimentin positivity. Five out of the 6 patients in whom the proliferation markers were obtained demonstrated a high proliferation index (Ki-67 labeling index, 20–50%). The mean length of survival in the group was 4.6 years (range 1 month to 16 years). Children who presented in the 1st year of life had shorter survival than those who presented at an older age. Six patients (40%) had cerebrospinal fluid (CSF) dissemination of the tumor. CSF dissemination was associated with a shorter mean survival of 1.9 years.Conclusions Our review of this series of patients indicates the requirement for adjuvant therapy and for continued efforts to classify tumor subtypes aimed at optimizing future treatments for patients with a primary CNS sarcoma.An erratum to this article can be found at     

Cerebrovascular disease in sickle cell anemia: a clinical, pathological and radiological correlation

An opportunity to study cerebrovascular changes in sickle cell anemia (SCA) presented itself when a black child with this disorder died of bihemispheric strokes. Angiography demonstrated severe occlusive vascular disease involving primarily the circle of Willis and major bifurcations of both internal carotid arteries. Collateral circulation to the distal branches of the internal carotid arteries occurred through transdural anastomoses from the external carotid system and via the leptomeningeal route. Perfusion of the basal ganglia was accomplished by vessels arising from the proximal internal carotid arteries. These changes resembled those of Moyamoya disease. Autopsy showed old and recent cerebral infarcts. Two vascular processes were responsible for the arterial occlusions: (1) exuberant intimal hyperplasia, and (2) old and recent thrombi with partial recanalization. The former has been described only once before in SCA. Small vessels in the basal ganglia were exceptionally numerous and dilated. We conclude that intimal hyperplasia within large cerebral arteries may be responsible for infarction and small vessel prliferation in basal ganglia in patients with SCA.     

Desmin-related myopathy: clinical, electrophysiological, radiological, neuropathological and genetic studies

Ten Spanish patients from six unrelated families diagnosed with desmin-related myopathy (DRM) were studied. The pattern of DRM inheritance was autosomal dominant in three families, autosomal recessive in one, and there was no family history in two cases. The disease onset was in early adulthood. Cardiac myopathy was the initial presentation in two patients, respiratory insufficiency in one, and lower limb weakness in all others. Cardiac involvement was observed in four patients. Lens opacities were found in four. CK level was normal or slightly elevated, and electrophysiological examination was consistent with myopathy. Muscle biopsies identified intracytoplasmic desmin-immunoreactive inclusions. In addition to desmin, synemin, actin, gelsolin, ubiquitin, alphaB-crystallin and amyloid betaA4 were also present in the deposits. Ultrastructural examination revealed areas of myofibrillary disruption, abnormal electron-dense structures and accumulations of granulofilamentous material. A missense R406W mutation and a novel single amino acid deletion in the desmin gene were identified in two patients; the other patients did not show mutations in desmin, synemin, syncoilin or alphaB-crystallin genes. Analysis of 10 Spanish DRM cases illustrates a wide clinical, myopathological and genetic spectrum of DRM, reinforcing the need for further exploration of genetic causes for this group of disorders.     

Hereditary motor and sensory neuropathy-Lom (HMSNL) in a Spanish family: clinical, electrophysiological, pathological and genetic studies

The clinical, electrophysiological, pathological and genetic findings are described in the first Spanish family diagnosed with hereditary motor and sensory neuropathy type Lom (HMSNL) initially identified by Kalaydjeva et al. in 1996. The three affected patients belong to a non-consanguineous family with Gypsy background that were followed up over 10 years. Serial clinical and neurophysiological examinations and genetic analysis were undertaken in every patient. Sural nerve biopsy was performed in the oldest patient. The clinical features are similar to those previously described in HMSNL and all of them showed abnormal brain auditory evoked potentials. The oldest brother developed sensorineural deafness at the age of 20. Conduction velocities were unobtainable in all patients and nerves tested except for the median nerve in the youngest child in whom conduction was severely slowed. Neuropathological examination revealed a severely depleted nerve with very few surviving myelinated fibers which possessed thin myelin sheaths. Schwann cell processes were arranged in circular configurations without typical onion bulb configuration. Genetic analysis showed that the maternal chromosome inherited by all three affected siblings displayed a very unusual haplotype. Our patients show the characteristic clinical, electrophysiological and pathological findings described in HMSNL and represent the first reported Spanish family affected from the disease. The genetic findings in this family have contributed to refine the HMSNL critical linkage region.     

Germanium myopathy: clinical and experimental pathological studies

Summary Pathological examinations were carried out on the skeletal muscle of a patient with germanium intoxication. The prominent histochemical finding was vacuolar myopathy with lipid excess, increased acid phosphatase activity and decreased cytochrome c oxidase activity. Ultrastructural lesions revealed a mitochondrial abnormality, autophagic vacuoles and accumulation of high electron-dense materials in deformed mitochondria and at the periphery of lipid droplets. Furthermore, the toxic effect of germanium on skeletal muscle was confirmed by the experimentally induced germanium myopathy, which showed autophagic degeneration, decreased cytochrome c oxidase activity and a mitochondrial abnormality with high electron-dense materials.