Peri-ictal water drinking and other ictal vegetative symptoms: Localizing and lateralizing the epileptogenic zone in temporal lobe epilepsy? Two case reports and review of the literature.

Peri-ictal behavior disorders can be helpful in localizing and lateralizing seizure onset in partial epilepsies, especially those originating in the temporal lobe. In this paper, we present the case of two right-handed women aged 36 and 42 years who presented with partial seizures of mesial temporal type. Both of the patients had drug resistant epilepsy and undergone presurgical evaluation tests including brain magnetic resonance imaging, video-EEG monitoring and neuropsychological testing. The two patients had hippocampal sclerosis in the right temporal lobe and exhibited PIWD behavior concomitant with right temporal lobe discharges documented during video-EEG recordings. Anterior temporal lobectomy was performed in one case with an excellent outcome after surgery. The patient was free of seizures at 3 years follow-up. We reviewed other publications of peri-ictal autonomic symptoms considered to have a lateralizing significance, such as peri-ictal vomiting, urinary urge, ictal pilo-erection. Clinicians should search for these symptoms, even if not spontaneously reported by the patient, because they are often under-estimated, both by the patients themselves and by physicians. Additionally, patients with lateralizing auras during seizures have a significantly better outcome after epilepsy surgery than those without lateralizing features.

[Congenital insensitivity to pain: clinical and neurophysiological study in three sisters of a Moroccan family]. / Insensibilité congénitale à la douleur, étude clinique et neurophysiologique chez 3 sœurs marocaines.

Congenital insensitivity to pain is a rare hereditary sensory and autonomic neuropathy (HSAN). This disorder is an autosomal recessive condition: since 1996, mutations attributed to this entity have been found in the neurotrophin tyrosine-kinase gene receptor on chromosome 1. The authors report 3 cases of congenital insensitivity to pain. In these 3 sisters of consanguineous parents, the clinical investigation showed total absence of pain and temperature sensations with preservation of all other sensory modalities, mental retardation, but in contrast to HSAN type IV, there was no anhidrosis. The neurophysiological investigation revealed an isolated axonal sensory polyneuropathy in the 3 patients. The clinical and neurophysiological investigations were normal in both parents and the brother. The physiopathology of this entity is discussed. We suggest a particular form of HSAN type IV with preservation of transpiration or a new entity of congenital insensitivity to pain, which should be analyzed genetically.

[T-cell lymphoma revealed by a mononeuritis multiplex: case report and review of literature]. / Lymphome T révélé par une mononeuropathie multiple: étude d'un cas avec revue de la littérature.

INTRODUCTION: Lymphoma occasionally affects the peripheral nervous system. Neuropathy usually appears in patients with known lymphoma but rarely represents the initial manifestation of underlying malignancy. We report a case in which mononeuritis multiplex (MM) was the dominant feature in the clinical presentation of a peripheral T-cell non-Hodgkin lymphoma (NHL). OBSERVATION: A 32-year-old man suffered from an asymmetric progressive sensory-motor peripheral neuropathy. The left peroneal nerve was affected first, then the left median nerve after one month, followed by the left trigeminal nerve ten months later. The electrophysiological study confirmed the diagnosis of axonal sensory-motor MM. Mediastinal adenopathies, splenomegaly, pancytopenia and inflammatory syndrome were also found. An osteo-medullary biopsy showed a T-cell NHL. Nerve biopsy study found an inflammatory lymphoid infiltration without malignant cell supporting the hypothesis of an inflammatory pathogenic process. Chemotherapy including cyclophosphamide, hydralazine, vincristine and prednisone were administered monthly during 8 months. No improvement was obtained. DISCUSSION: It must be emphasised that this case is an uncommon one. On the one hand, NHL is rarely associated with MM and on the other hand, it can exceptionally be revealed by a MM. We were able to find 30 reported cases of distal neuropathy revealing a NHL including, 8 mononeuritis simplex, 9 MM and 13 polyneuropathies. Polyradiculoneuritis cases were excluded from this study because the neuropathy is usually caused by a meningeal infiltration. The neuropathy was in the majority of the cases chronic and axonal. The lymphoma was more often B-cell than T-cell. The B-cell lymphoma was frequently associated with a poor prognosis. All mechanisms were present with a predominance of neurolymphomatosis.

Drug resistance and hippocampal damage after delayed treatment of pilocarpine-induced epilepsy in the rat.

Temporal lobe epilepsy (TLE) is the most common and pharmacoresistant form of epilepsy. Problems that cause pharmacoresistance may include delayed therapy due to late consultation, especially in developing countries. Our study aimed at unraveling consequences of delayed drug treatment using a rat model of TLE. Following pilocarpine-induced status epilepticus interrupted after 4h, rats were continuously videorecorded for onset and recurrence of spontaneous convulsive seizures. The animals were then treated for 50 days with carbamazepine (CBZ; first-line drug in TLE and effective also in rats), starting at seizure onset (27.22+/-3.38 days after status epilepticus) or 50 days later, and compared with epileptic untreated rats and non-epileptic CBZ-treated ones. Convulsive seizure frequency and duration, and hippocampal cell changes were evaluated. In particular, parvalbumin-containing hippocampal interneurons, astrocytes and microglia were characterized with immunohistochemistry and quantitative analyses. Prompt administration of CBZ suppressed seizures; delayed treatment only decreased frequency of convulsive seizures, which were also relatively prolonged. In hippocampal regions, histopathological damage, parvalbumin immunoreactivity loss, and glial activation were very marked after delayed treatment, and were reduced only slightly compared to untreated epilepsy, but enhanced compared to early treatment. The data on high frequency and duration of convulsive seizures in late-therapy rats indicate that delayed CBZ administration caused a high degree of drug resistance. This condition was subserved by severe damage in the hippocampus, presumably consequent to long-term seizure recurrence. Overall the data indicate that the paradigm of delayed treatment of limbic epilepsy could provide a model of drug-refractory TLE with hippocampal sclerosis.

High incidence of SMN1 gene deletion in Moroccan adult-onset spinal muscular atrophy patients.

Spinal muscular atrophy (SMA) is an autosomal recessive motor neuropathy characterized by selective degeneration of anterior horn cells of the spinal cord. Childhood SMA is divided into three types (I-III) on the basis of age of onset and severity. These disorders have been linked to the 5q13 region, where mutations in the Survival Motor Neuron 1 (SMN1) gene have been found in affected individuals. In the case of adult-onset SMA (type IV), on the other hand, reports of homozygous absence of SMN1 gene have been rare. We conducted deletion analysis of SMN and a neighboring gene, NAIP (neuronal apoptosis inhibiting protein). Among 54SMA patients (types I-IV), all of Moroccan origin, Exon 7 of the SMN1 gene was homozygously absent in 100% of type I, 90% of type II, 74% of type III and 80% of type IV SMA patients. Deletion of SMN1 exon 8 was detected in 100% of type I, 53% of type II, 53% of type III and 80% of type IV patients. NAIP exon 5 was homozygously deleted in 67% of type I, 32% of type II, 5% of type III and 20% of type IV SMA patients. Thirty control individuals who were studied had normal SMN1 and NAIP genes. Our results show a high incidence of SMN1 gene deletion in adult-onset SMA patients indicating that SMN1 is the autosomal recessive adult SMA-causing gene. While NAIP is commonly deleted in SMA, this is unlikely to affect disease severity; it was deleted in two adult SMA patients with mild phenotypes.

[Acute Guillain-Barré-like polyradiculoneuritis revealing acute systemic lupus erythematosus: two case studies and review of the literature]. / Polyradiculonévrite aiguë de type Guillain-Barré révélant un lupus érythémateux aigu disséminé: étude de deux cas et revue de la littérature.

The involvement of the peripheral nervous system in systemic lupus erythematosus (SLE) is rare and is dominated by distal symmetric axonal polyneuropathy and multiple mononeuropathy. It usually occurs in late course of the disease. Acute polyradiculoneuropathy of Guillain-Barré syndrome type is very rare and can frequently constitute the first symptom of systemic lupus. We report two cases of acute inflammatory demyelinating polyradiculoneuropathy (AIDP) complicated by respiratory failure due to systemic lupus. In the first case, the pure motor AIDP was the first manifestation of the SLE. The outcome under prednisone treatment was dramatically good with regression of clinical deficit and normalisation of nerve conduction within one month and 12 months of treatment respectively. In the second case the AIDP occurred only one week after diagnosis of SLE and corticotherapy. It was a demyelinating sensory-motor neuropathy. Clinical improvement was obtained after two cures of intravenous gammaglobulin (IVIg). The normalisation of nerve conduction was obtained within 8 months. AIDP is a very rare complication of SLE, but it should be searched as an aetiology of Guillain-Barré syndrome associated to systemic clinical symptoms or to blood inflammation. Corticotherapy could be sufficient, but in some cases the addition of IVIg or plasmapheresis might be necessary.

[Late discovery of Lafora disease: a family study]. / La maladie de Lafora à révélation tardive.

Lafora disease is a progressive myoclonic epilepsy, Clinically defined by the association of myoclonic, epileptic fits and dementia. We report a case with an atypical Lafora disease, marked by delayed onset at 25 years of age, prolonged course, associated with secondary cognitive impairment and myoclonic features.

[Epileptic seizures and epilepsy in subacute sclerosing panencephalitis (report of 30 cases]. / Crises épileptiques et épilepsie dans le cadre d'une panencéphalite sclérosante subaiguë (à propos de 30 cas).

Subacute Sclerosing Panencephalitis (SSPE) is becoming less frequent in Morocco since the generalization of measles vaccination in 1982. The aim of this study was first to analyze the semiological and elecrophysiological profiles of epilepsy in SSPE in both 'disease-revealing' seizures and sequellar ones, and second, to study the evolution of epilepsy and its possible prognostic value in SSPE. Among the neurological manifestations of SSPE, epilepsy is not as rare as frequently reported in the literature. In this longitudinal series concerning 70 cases of SSPE, 30 developed epilepsy. In two-thirds of our patients the epileptic seizures started in the first year of evolution; they revealed the SSPE in 23% of the cases and were sequellar in the rest. Seizures revealing the SSPE were widely dominated by partial seizures, secondarily generalized or not (86%), suggesting a focalized encephalitic process. Conversely, sequellar seizures were in most cases generalized tonic-clonic (43%), and therefore compatible with an already spread process. The EEG contributed both to the diagnosis of SSPE and to that of the epilepsy, showing epileptic abnormalities in ten patients. The outcome of epileptic seizures was very favorable under antiepileptic drugs, while that of SSPE remained severe and not modified by epilepsy. The authors underline the relative frequency of epilepsy in SSPE, the interest of the distinction between revealing and sequellar seizures, the good prognosis of epilepsy under adequate therapy, and the absence of prognostic value of epilepsy in SSPE.

Vitamin E deficiency ataxia associated with adenoma.

Vitamin E is one of the most important lipid-soluble antioxidant nutrient. Severe vitamin E deficiency (VED) can have a profound effect on the central nervous system. VED causes ataxia and peripheral neuropathy that resembles Friedreich's ataxia. We report here a patient presenting this syndrome, but also a prolactin and FSH adenoma. Both the neurological syndromes and the adenoma regressed after treatment with alpha-tocopherol. Although, the presence of the prolactinoma in this patient may not be related to his vitamin E deficiency, alpha-tocopherol treatment seems to be beneficial and might usefully be tested in patients with hypophyseal secreting other forms of adenoma.

A PCR amplification method reveals instability of the dodecamer repeat in progressive myoclonus epilepsy (EPM1) and no correlation between the size of the repeat and age at onset.

Progressive myoclonus epilepsy of the Unverricht-Lundborg type (EPM1) is a rare, autosomal recessive disorder characterized by onset at age 6-16 years, generalized seizures, incapacitating myoclonus, and variable progression to cerebellar ataxia. The gene that causes EPM1, cystatin B, encodes a cysteine proteinase inhibitor. Only a minority of EPM1 patients carry a point mutation within the transcription unit. The majority of EPM1 alleles contain large expansions of a dodecamer repeat, CCC CGC CCC GCG, located upstream of the 5' transcription start site of the cystatin B gene; normal alleles contain two or three copies of this repeat. All EPM1 alleles with an expansion were resistant to standard PCR amplification. To precisely determine the size of the repeat in affected individuals, we developed a detection protocol involving PCR amplification and subsequent hybridization with an oligonucleotide containing the repeat. The largest detected expansion was approximately 75 copies; the smallest was approximately 30 copies. We identified affected siblings with repeat expansions, of different sizes, on the same haplotype, which confirms the repeat's instability during transmissions. Expansions were observed directly; contractions were deduced by comparison of allele sizes within a family. In a sample of 28 patients, we found no correlation between age at onset of EPM1 and the size of the expanded dodecamer. This suggests that once the dodecamer repeat expands beyond a critical threshold, cystatin B expression is reduced in certain cells, with pathological consequences.

Allelic heterogeneity of Mediterranean myoclonus and the cystatin B gene.

Mediterranean myoclonus is a progressive myoclonus epilepsy with autosomal recessive inheritance. Another form has been described in Finland, the so-called Baltic myoclonus. Mediterranean myoclonus and Baltic myoclonus are also known as Unverricht-Lundborg disease. Linkage analyses have shown that the genes for both these forms of myoclonus are closely linked to 21q22.3 DNA markers, suggesting that they are caused by mutations at the same locus (EPM1). Recently, two heterozygous mutations were found in the cystatin B gene in patients with Unverricht-Lundborg disease. We report recombinational and linkage disequilibrium mapping of EPM1, and cystatin B gene sequencing, in 14 consanguineous pedigrees with Mediterranean myoclonus. Linkage to 21q22.3 DNA markers was observed in all these families. Haplotype analysis suggests that a common mutation segregates within these pedigrees, and that this mutation is different from the common one responsible for the Finnish form of Unverricht-Lundborg disease. No mutation was found in the exons or splice junctions of the cystatin B gene in the 14 pedigrees.

Identification of mutations in cystatin B, the gene responsible for the Unverricht-Lundborg type of progressive myoclonus epilepsy (EPM1).

Progressive myoclonus epilepsy (EPM1) is an autosomal recessive disorder, characterized by severe, stimulus-sensitive myoclonus and tonic-clonic seizures. The EPM1 locus was mapped to within 0.3 cM from PFKL in chromosome 21q22.3. The gene for the proteinase inhibitor cystatin B was recently localized in the EPM1 critical region, and mutations were identified in two EPM1 families. We have identified six nucleotide changes in the cystatin B gene of non-Finnish EPM1 families from northern Africa and Europe. The 426G-->C change in exon 1 results in a Gly4Arg substitution and is the first missense mutation described that is associated with EPM1. Molecular modeling predicts that this substitution severely affects the contact of cystatin B with papain. Mutations in the invariant AG dinucleotides of the acceptor sites of introns 1 and 2 probably result in abnormal splicing. A deletion of two nucleotides in exon 3 produces a frameshift and truncates the protein. Therefore, these four mutations are all predicted to impair the production of functional protein. These mutations were found in 7 of the 29 unrelated EPM1 patients analyzed, in homozygosity in 1, and in heterozygosity in the others. The remaining two sequence changes, 431G-->T and 2575A-->G, probably represent polymorphic variants. In addition, a tandem repeat in the 5' UTR (CCCCGCCCCGCG) is present two or three times in normal alleles. It is peculiar that in the majority of patients no mutations exist within the exons and splice sites of the cystatin B gene.