Significance of tuber size for complications of tuberous sclerosis complex.

INTRODUCTION: Tuberous sclerosis complex (TSC) is one of the most frequent neurocutaneous disorders. Cortical tubers are the most common pathological changes in TSC and they are directly related to the disease's main clinical manifestations: seizures, mental retardation, and autistic behaviour. OBJECTIVE: The aim of this study is to establish a correlation between tuber size and the severity of clinical features in TSC. MATERIAL AND METHODS: We performed a retrospective study of the clinical and imaging findings from 45 TSC patients (22 females and 23 males) and compared the clinical features with the location, size, and number of the cortical tubers in each patient. RESULTS: Four patients had voluminous tubers located in 1 or both cerebral hemispheres. All of these patients had intractable seizures and severe mental retardation; 3 of these cases also presented with autistic behaviour, despite tubers having been resected in all 4 patients. Thirteen patients had tubers of large-to-average size, and all patients in this group showed intractable seizures and mental retardation. Nine patients who had experienced infantile spasms during the first year of life presented autistic behaviour. Multiple tubers of small to average size were found in 28 patients. In general, this group had seizures that responded well to antiepileptic drugs and a low prevalence of autism. In 3 patients who all presented good seizure control and normal intelligence, single cortical/subcortical tubers were located in the frontal or occipital lobes. Of the total of 45 patients, 13 had cerebellar as well as cerebral tubers; these were generally present in cases with more severe clinical features. CONCLUSIONS: Although large tubers are less common than small to medium-sized ones, they are much more likely to be accompanied by severe clinical symptoms (seizures, mental retardation and autistic behaviour), even when the smaller tubers are quite numerous.

Focal cortical dysplasia. Clinical-radiological-pathological associations.

INTRODUCTION: The term focal cortical dysplasia (FCD) describes a particular migration disorder with a symptomatology mainly characterised by drug-resistant epileptic seizures, typical neuroradiological images, and histological characteristics, as well as a very positive response to surgical treatment in the majority of cases. MATERIAL AND METHODS: A total of 7 patients were studied, comprising 6 children with a mean age of 34.3 months and one 25-year-old male with very persistent focal seizures and MRI images that showed FCD. RESULTS: Three of the patients (all girls) were operated on while very young, with extirpation of the FCD and the surrounding area; with the histopathology study showed agreement between the MRI images and the macroscopic study of the slices. The histology study showed findings typical of a Taylor-type FCD (poor differentiation between the cortical grey matter and the subcortical white matter, and balloon cells). Three years after the FCD extirpation, the same 3 patients remained seizure-free with no anti-epilepsy medication. Two others have seizure control with medication, another (the adult) is on the surgical waiting list, and the remaining patient refused the operation. CONCLUSION: Taylor-type FCD is associated with a high percentage of all drug-resistant focal seizures, and it needs to be identified and extirpated as soon as possible. Well planned and well-performed surgery that leaves no remains of dysplasia can cure the disease it in many cases.

[Solitary fibrous tumors of the meninges: report of three cases and literature review]. / Tumor fibroso solitario meníngeo: descripción de tres casos y revisión de la literatura.

We report 3 patients with fibrous solitary tumor of meningeal location where we described the histological study, as well as evolution after the surgical treatment. The described patients presented ages of 37, 52 and 65 years, after the resection has not appeared an objective sign of recurrence in any case after 4, 6 and 7 years of follow-up respectively. Checking the literature the tumor is indistinguishable clinical and radiolocally of the typical meningioma, doing necessary the use of inmunohistochemistry to do the differential diagnosis, where positiveness for CD34 and the negativeness for EMA define the fibrous solitary tumor. It is about a benign tumor, where total removing is the principal factor in prognosis, nevertheless there are cases of local recurrences and long-distance metastasis. We can find all these characteristics in the showed cases of the present article, having the uncertainty of its local or systemic relapse ability in the future.

[Cerebellar ataxia of Norman-Jaeken. Presentation of seven Spanish patients]. / Ataxia cerebelosa de Norman-Jaeken. Presentación de siete pacientes españoles.

AIM: To show that the cerebellar ataxias described by Norman and by Jaeken (CDG1a) are the same disease. PATIENTS AND METHODS: Seven patients, five females and two males (there were two siblings pairs), who presented a severe cerebellar disease slowly progressive associated with generalized cerebellar atrophy. The sister of one of the patients of the series had been studied because of psychomotor retardation but she died at two years of age due to respiratory problems. An autopsy was carried out that showed severe cerebellar atrophy, and the histological study revealed loss of granular cells and diverse abnormalities of Purkinje's cells, especially focal swellings of 'asteroid bodies' or 'cactus like' type. This suggested to us that Norman's ataxia and CDG1a could be the same pathological entity. RESULTS: All seven patients had severe cerebellar hypoplasia-atrophy and a small brainstem. Most patients showed peripheral neuropathy with decreased motor nerve conduction velocity, but very little decreased sensory nerve conduction velocity. All seven patients had highly raised serum concentrations of asialotransferrin, and heterozygous molecular PMM2 deficit (CDG1a). One of these seven cases was the patient whose sister had histological cerebellar changes corresponding to Norman's ataxia. CONCLUSION: The findings observed in our series suggest that the diseases described by Norman and Jaeken are the same pathological entity and CDG1a can be the biological basis of the histological changes of the cerebellum in Norman's ataxia. We suggest the name of Norman-Jaeken ataxia or disease for this entity.

[Mitochondrial respiratory chain diseases. Evaluation and variability in 52 patients]. / Enfermedades de la cadena respiratoria mitocondrial. Evaluación y variabilidad en 52 pacientes.

INTRODUCTION: Clinical, electrophysiological, genetic and biochemical deficiencies variability were evaluated in 52 patients diagnosed of mitochondrial respiratory chain diseases (MRCD). PATIENTS AND METHODS: 26 men and 26 women, aged 19 to 79 years, were tested by clinical examination, electrophysiological techniques, muscle biopsy and genetic and biochemical studies. RESULTS: The patients were classified into seven phenotypes: myopathy, chronic progressive external ophthalmoplegia, progressive ophthalmoplegia plus ataxia, Kearns-Sayre syndrome, mitochondrial encephalomyopathy with lactic acidosis and stroke episodes (MELAS), myoclonic encephalopathy with ragged-red fibers (MERRF), and encephalopathies. Each phenotype may begin by different ways. The electromiography showed myopathy in 39 cases and various types of neuropathy in 10. Ragged-red COX negative fibers or widespread electron microscopic abnormalities were found in 47 cases. Simple deletions, multiple deletions and three different point mutations were observed. Deficiency of complexes I, II, III and IV were found alone or in different associations. CONCLUSIONS: MRCD shows wide variations in clinical, genetic and biochemical studies. Some patients with nonspecific manifestations, mainly of central nervous system, need careful attention and to be on account of diagnostic suspicion.

Multiple intraspinal low-grade astrocytomas mixed with lipoma (astrolipoma). Case report.

Multiple intraspinal low-grade astrocytomas without neurofibromatosis stigmata and low-grade astrocytoma with intermingled areas of adipose tissue have not been reported previously. The authors present the case of a 48-year-old woman with a 7-month history of paraparesis. When she underwent surgery, multiple intraspinal mixed tumors made up of astrocytes mingled with adipose cells were found and excised. In this report, the authors refer to this tumor as an "astrolipoma" and discuss its characteristics.

Can nimodipine prevent ischaemic reperfusion injury in the rat brain?

Reperfusion injury is a pathophysiological entity distinct from the primary ischaemic injury; the oxygen arriving with blood recirculation, although necessary for alleviating the ischaemic status, may be harmful and provoke additional injury in the already damaged tissue. This study aims to analyse whether nimodipine reduces cerebral dysfunction after transient global cerebral ischaemia, using our previously described experimental model, which permits the impregnation of cerebral tissue during the periods of ischaemia and reperfusion. Some aspects of this study contribute to our understanding of the reperfusion injury concept. Three groups of rats were used. Animals in Group 1 (n = 13) served as normal controls for neurophysiological recordings. Rats in Groups 2 (n = 7) and 3 (n = 7) were subjected to global cerebral ischaemia and either isotonic saline (Group 2) or nimodipine solution (Group 3; 40 micrograms/kg) was intra-arterially injected through the external carotid artery during ischaemia and reperfusion and distributed to the circle of Willis. Seventy-two hours after global cerebral ischaemia somatosensory evoked potentials were evaluated and P1 wave latency was used to compare the three groups of animals. The peak onset of this wave was 8.13 +/- 1.5 msec, 18.63 +/- 3.1 msec and 13.17 +/- 2 msec for Groups 1, 2 and 3 respectively. P1 latency was significantly higher in Group 2 than in Groups 1 and 3 (p < 0.01). Histopathological findings showed that the level of injury in the hippocampus and striatum in Group 3 was more limited than in Group 2, although no statistical significance could be found.(ABSTRACT TRUNCATED AT 250 WORDS)

[Multifocal polyneuropathy with persistent conduction blockage. A new subset of chronic inflammatory polyneuropathies]. / Polineuropatía multifocal con bloqueos de conducción persistentes. Un nuevo subgrupo dentro de las polineuropatías inflamatorias crónicas.

Recently a subset of chronic demyelinating inflammatory polyneuropathies with asymmetrical involvement limited to upper limbs, at least at the onset, resembling a multifocal mononeuropathy has been described. Electrodiagnostic testing disclosed multifocal CB outside the common entrapment sites has been described. We report a 55 years old man with a 4 years history of paresis, numbness, fasciculations, myokymia, cramps and mild amyotrophy. Electrophysiological evaluation showed proximal multifocal conduction block and abundant spontaneous activity as fasciculations, myokymia and scarce denervation activity. The importance of taking into account this entity in the differential diagnosis of patients with suspected mononeuritis multiplex or motoneuron disease is emphasized. The nosologic place of this entity is also discussed.

Single fiber electromyography (SFEMG) in mitochondrial diseases (MD).

Conventional EMG, nerve conduction studies and SFEMG were performed in 18 patients with various phenotypes of MD. 14 cases showed findings consistent with mild myopathy, 2 patients signs of sensory-motor axonal neuropathy and 2 cases a mixture of myopathy and axonal neuropathy. Motor unit fiber density was mild increased in 8 out of 13 tested cases. Jitter was abnormal in 10 out of 18 tested patients. Jitter abnormalities were not related to myopathic or neurogenic features in the EMG study, and may be observed in muscles without clinical weakness. The results suggest the existence of neuromuscular transmission disturbances in patients with MD.

[Schilder's diffuse myelinoclastic sclerosis]. / Esclerosis mielinoclástica difusa de Schilder.

OBJECTIVE: The aim of this study is to analyze clinical features, neuroradiological findings and evolution associated with Schilder s disease (SD). PATIENTS AND METHODS: We describe 5 cases (4 female/1 male) diagnosed of SD. Clinical characteristics, neuroimaging (CT and MRI), EEG, evoked potential analysis (4/5) and laboratory tests are provided, including the level of serum very long chain fatty acid of plasma cholesterol esters (3/5). RESULTS: Patients were aged between 7 and 12 years. The first clinical manifestations were: hemiparesis (3/5), quadriparesis dysarthria (1/5), and seizures cerebellar dysfunction (1/5). Other clinical features were: partial seizures (3/5), cerebellar dysfunction (2/5), loss of sensibility (3/5), visual loss (1/5), and dysarthria (2/5). CT scan and MRI showed large zones of hypodensity in the hemispheric white matter (4/5) with enhancement in T2 weighted MRI images. This finding was also observed in medulla (1/5) and cerebellum (1/5). Laboratory data were normal. EEGs showed general slow background patterns in all cases. Abnormal evoked potential analysis were recorded in 3 children. Clinical improvement followed the steroid therapy in all cases. Clinical evolution was: minimal motor disabilities (5/5), recurrences (3/5), controlled seizures (3/3), and psychomotor retardation (1/5). CONCLUSIONS: SD is a rare demyelinating disorder, with a probable relationship to multiple sclerosis. The course of this disease is unpredictable; recurrences may appear and sequelae are frequently observed. Diagnosis should be based on clinical features, neuroradiological findings and evolution.

[Lafora disease. A new case of confirmation of diagnosis on molecular genetic studies]. / Enfermedad de Lafora. Confirmación diagnóstica por genética molecular de un nuevo caso.

INTRODUCTION: Lafora s disease is a type of progressive myoclonic epilepsy with bad prognosis. Until now diagnosis was based on finding characteristic intracytoplasmatic polyglucosan bodies in biopsies of sweat secreting cells in the skin. Recently the gene responsible has been discovered. This permits firm diagnosis and screening of carriers. We present the case of a child diagnosed on molecular genetic studies. CLINICAL CASE: A 12 year old boy with a clinical history of three febrile seizures at the age of one year but no other abnormalities, presented a seizure of visual disorder with secondary generalization. There was no family history of seizures. Following a period of normality he had further seizures (clonic, visual and generalized myoclonic). The EEG showed generalized spike and wave activity, which was more marked after stimulation by light and became progressively worse. Neuroimaging studies were normal. In spite of treatment there was a progressive increase in visual and generalized myoclonic seizures together with deterioration of cognitive function and ataxia. Histological studies of the sweat glands showed homogeneous nodular deposits of intracytoplasmatic PAS+. Molecular studies of the EPM2A gene linked to chromosome 6q24 showed the presence of two mutations on the 1 and 4 exons. CONCLUSIONS: We describe a 12 year old patient with all the clinical features of Lafora type progressive myoclonic epilepsy in whom characteristic cytoplasmic bodies were found in the sweat gland biopsy. Molecular genetic studies of the EPM2A gene confirmed diagnosis of the disorder.

[Menkes' disease: anatomo-clinical presentation of a case]. / Enfermedad de Menkes: presentación anatomoclínica de un caso.

We describe a case of Menke's disease with severe neurological involvement, convulsive crises and characteristic hair anomalies (scanty, fragile, macroscopically hypopigmented and microscopically kinked) which led to rapid diagnosis. Vascular abnormalities with elongated, twisted arteries, skeletal abnormalities (more wormian cranial bones than usual, lateral spurs of metaphyses) and vesicle diverticuli. Electron microscopy of skeletal muscle showed concentrically laminated bodies, possibly of mitochondrial origin. Respiratory chain enzyme activity was normal. The patient died at the age of two and a half. On necropsy, histological abnormalities characteristics of the illness were seen (loss of neurones in the granular layer of the cerebellum, the neurones of Purkinje had thickening of the dendrites which spread out in the form of a weeping willow, reduplication and fragmentation of the internal elastic layer of muscle arteries). In the cortex of the cerebellum mega-mitochondria with electron-dense bodies, were seen on electron microscopy. This is the first case of Menke's disease described in the Spanish literature which includes pathology and electron microscope studies.

[Subependymal giant cell astrocytoma in tuberous sclerosis complex. A presentation of eight paediatric patients]. / Astrocitoma subependimario de células gigantes en el complejo de esclerosis tuberosa. Presentación de ocho pacientes infantiles.

OBJECTIVE: Presentation of 8 patients with subependymal giant-cell astrocytomas (SGCA) associated with tuberous sclerosis complex (TSC). MATERIAL AND METHODS: There are 8 patients, 6 males and 2 females with TSC, who presented with the tumour between the neonatal period and 24 years. RESULTS: All patients showed bilateral hypersignalised areas in zones close to the foramen of Monro. Three of the patients were admitted urgently due to blindness and increased intracranial pressure. Incomplete removal of the tumour has always been bad solution as it resulted in the death of the patient (in one case) or further surgery operation in the short term. Only one patient developed the tumour suddenly from pre-existing subependymal nodules from the childhood and they had to be removed at 24 years of age. By contrast, 32 patients with TSC and images of subependymal nodules whose CT or MR progress was followed up for between 10 and 30 years did not develop a tumour. One patient had to be operated four times over 20 years. CONCLUSIONS: SGCA associated with TSC is a severe complication which as likely to develop and careful monitoring is required from neonatal age with periodicclinical and imaging studies in order to avoid its irreversible complications. Hydrocephaly, blindness and even the death can be the main consequences. Reintervention of the recurrent tumour is often necessary.

[Opsoclonus-myoclonus-ataxia syndrome: two anatomo-clinical case reports]. / Sindrome opsoclono-mioclono-ataxia: dos casos anatomoclinicos.

INTRODUCTION: Opsoclonus-myoclonus-ataxia syndrome (OMAS) is characterised by the acute or subacute development of chaotic eye movements and diffuse myoclonus. On some occasions it is associated with ataxia and encephalopathy. In adults there are multiple causations and a possible paraneoplastic origin must always be taken into account. CASE REPORTS: We report two cases of OMAS of a paraneoplastic origin with a post mortem study. In the first case, the syndrome was associated to a small-cell carcinoma in the lungs, and in the second patient it was associated to a digestive lymphoma. Neuroimaging studies did not reveal any kind of alterations in either of the two cases. In our cases, none of the antibodies that are relatively frequently associated to this syndrome were found. In both of them, an immunomodulator treatment regimen was established; only the patient with the lymphoma showed an initial improvement with antineoplastic therapy. In the pathological study, alterations were observed in the brain stem, and in the second patient alterations were also found in the cerebellum. CONCLUSIONS: This is a rare condition that obliges the specialist to think in order to reach a correct diagnosis, and to search for the primary tumour and establish early treatment in order to bring about an improvement and even the remission of the neurological signs and symptoms. The pathological findings are not pathognomonic, but they are typical of this syndrome.

[Muscle-eye-brain disease. Presentation of one case with genetic study]. / Trastorno músculo-ojo-cerebro. Presentación de un caso con estudio genético.

INTRODUCTION: The objective [corrected] is to present a case of muscle-eye-brain (MEB) disease with genetic study. MATERIAL AND METHODS: We studied an affected male from the age of 7 months to 21 years. During this time, clinical, analytical, neurophysiological (EEG, EMG, visual evoked potential [VEP], electroretinogram [ERG]), image (CT, MR), cerebral biopsy and genetic studies were performed. RESULTS: Severe visual acuity impairment with optic atrophy from the first months of life, abnormal VEP and ERG, CT and MR showing <> image of the cerebral cortex and subcortical white matter with myelinating changes; the histologic study of the cerebral biopsy sample showed hypomyelinating lesions and migration changes. The patient is alive at 21 years of age. The genetic study confirmed the presence of two recessive mutations, c.1274G>C and c.1895+1_4delGTGA, within the POMGnT1 gene. CONCLUSIONS: The patient shows typical clinical, neurophysiological, histological and genetic MEB features.

Vacuolating megalencephalic leukoencephalopathy: 24 year follow-up of two siblings.

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is an autosomal recessive disorder with a chronic progressive course. The gene, MLC1, has been localized on chromosome 22qtell and 26 different mutations have been described. We report two siblings of non-consanguineous parents who presented with characteristic features of MLC. They showed macrocephaly from the first months of life. After a short time, motor clumsiness, ataxia, seizures and psychomotor retardation were observed. During childhood, both patients had a coma that lasted several days following a minor head trauma. The eldest sister experienced a permanent deterioration of the clinical picture after the coma. Epilepsy and electroencephalographic alterations were chronic, tending to improve during adulthood. Cerebral biopsy showed normal or minor changes in the cortical grey matter, and in the white matter gliosis, increased extracellular spaces and decreased numbers of fibres with thin myelin sheets. We have followed the patients during 24 years, from the ages of 4 and 8 years to the their present ages of 28 and 32 years. Clinical and neuro-imaging follow-up showed a chronic course with more prominent progression of the white matter abnormalities than of the neurological features. A homozygous mutation of the MLC1 gene was found in both siblings. The eldest patient, 32 years-old, needs a wheel-chair but has a good contact with the family and surrounding people. The youngest, 28-years-old, shows mild ataxia, spasticity and motor clumsiness, but she is able to participate in activities of daily life.

ANCA-associated vasculitis as paraneoplastic syndrome with colon cancer: a case report.

Coexistence of a vasculitis and a neoplastic disease is rare and the pathogenesis is unknown. Most of these associations refer to leukocytoclastic or poliarteritis nodosa (PAN)-type vasculitis and hematological malignancies. There are few reports of vasculitis in patients with solid tumours and there are also few reports of paraneoplastic ANCA-associated vasculitis. We report a case of p-ANCA-positive vasculitis with peripheral nerve involvement associated with a colon cancer. Vasculitis resolved after corticoid treatment and surgical removal of the tumour.

[Neuropathology of HIV encephalitis]. / Neuropathología de la encefalitis VIH.

Neuropathologic features of HIV encephalitis are described in 8 cases selected among 36 autopsies of AIDS patients. From an epidemiologic point of view, the author remarks that parenteral drug addict patients are as prone as male homosexual patients to get HIV encephalitis. The surprisingly low incidence of this illness, recorded in the epidemiologic bulletin of Health Ministry is pointed out. Clinicopathologically, the complex nosologic problem and terminologic confusion of AIDS dementia are discussed, as well as the different neuropathologic criteria used to define HIV encephalitis. The term "panencephalitis with multinucleated cells" is proposed to name the neuropathologic lesions of those patients with HIV dementia and who show multinucleated cells as histopathologic hall mark of HIV encephalitis on brain examination. Physiopathologic interpretation about how the HIV affects the CNS is analyzed. Recent etiopathogenic interpretations of HIV dementia are included.

Small arterial granular degeneration in familial Binswanger's syndrome.

A 55-year-old mildly hypertensive woman died after having developed a subcortical dementia during the past 9 years, with focal neurological signs. She presented at the age of 46 years with short episodes of dizziness and diplopia, suggesting that transient ischemic attacks involved the posterior fossa structures. Over the next 8 years, she developed difficulty in walking, urinary incontinence and seizures. On examination in 1989, she was severely demented. There was tetraparesis, bilateral arm and leg spasticity with hyperreflexia and bilateral Babinski signs. She showed epilepsia partialis continua involving the eyes, left hemiface and limbs. CT showed hypodensity of the white matter and lacunes in the basal ganglia and centrum semiovale, moderate hydrocephalus with cerebellar and cortical atrophy. Clinical and radiological features were similar to those of Binswanger's disease. Similar cases had occurred in the family affecting the patient's grandfather, father and two brothers, suggesting an autosomal dominant hereditary disease. Postmortem examination disclosed a Binswanger type of leukoencephalopathy caused by a peculiar microangiopathy characterized by a slightly basophilic small arterial granular degeneration of the medial sheath associated with the presence of ballooned smooth muscle cells with clear cytoplasm. Electron microscopic study revealed degenerative changes in the parietal vessels with notable increase of basal-membrane-type material and electron-dense granular deposits. These lesions could correspond to a specific familial pathology of the small arteries of the brain. They are identical to those reported in some patients with autosomal dominant inheritance. For other patients with similar clinical features and the same familial pattern, reported as "hereditary multi-infarct dementia'' and "chronic familial vascular encephalopathy'', there are no sufficient objective pathological facts to consider that they have the same disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebellar hypoplasia with heterotopic purkinje cells in the molecular layer and preservation of the granule layers associated with severe encephalopathy. A new entity?

We present the case of an infant girl, born to first cousins, with a clinical phenotype consisting of microcephaly, hypotonia, strabismus and severe psychomotor retardation. Magnetic resonance imaging (MRI) showed global cerebellar atrophy involving the vermis and both hemispheres. The patient's serum transferrin levels were consistently unremarkable. Cerebellar biopsy, performed at 13 months of age, revealed heterotopic Purkinje cells in the molecular layer, but preservation of the external and internal granular layers. To our knowledge, this histological pattern of cerebellar cortical disorganization has not been described previously. The consanguinity of the parents suggests an autosomal recessive inheritance.