Showing papers in "Acta Neurologica Belgica in 2000"

Pathophysiology of epilepsy

Abstract: This work reviews the current knowledge on epileptogenesis and pathophysiology of epilepsy. Recently, gene defects underlying four monogenic epilepsies (generalized epilepsy with febrile seizures, autosomal dominant nocturnal frontal lobe epilepsy, benign familial neonatal convulsions and episodic ataxia type 1 with partial seizures) have been identified, shedding new light on the pathophysiology of epilepsy as these diseases are caused by ion channel mutations. Although epileptic syndromes differ pathophysiologically, common ictogenesis-related characteristics as increased neuronal excitability and synchronicity are shared as well as mechanisms involved in interictal-ictal transition. Emerging insights point to alterations of synaptic functions and intrinsic properties of neurons as common mechanisms underlying hyperexcitability. This work also reviews the neurochemical mechanisms of epilepsy. An imbalance between glutamate and gamma-aminobutyric acid neurotransmitter systems can lead to hyperexcitability but catecholaminergic neurotransmitter systems and opioid peptides were shown to play a role in epileptogenesis as well. An overview of currently available anti-epileptic drugs and their presumed mechanisms of action is given as an illustration of the neurochemistry of epileptogenesis. Most anti-epileptic drugs exert their anti-epileptic properties through only a few neurochemical mechanisms that are meanwhile basic pathophysiological mechanisms thought to cause seizures.

The three responses of the blink reflex in adult and juvenile migraine.

Abstract: Recent theories about migraine pathogenesis have emphasized the role of the trigeminal system in the pathogenesis of migraine attacks (Moskowitz, 1997). The blink reflex (BR) could be a suitable method to evaluate the trigeminal system in migraine, as it is generally elicited by stimulation of the trigeminal ophthalmic division (Kimura et al., 1967), involved in migraine attacks. Sixty one adult and 15 juvenile migraine without aura subjects were selected, in order to evaluate the BR features, including the subjective perceptive and pain thresholds and the R1, R2 and R3 components intensity thresholds and amplitudes. The electrophysiological procedure was carried out during the pain free phase. The findings were compared with those of 28 healthy controls, 18 adults and 10 children. In both adult and juvenile migraine sufferers an early appearance of the R3 response at almost the R2 threshold was observed in comparison with age-matched controls. Unfortunately, the anatomic and physiologic organization of the R3 component is uncertain: its early onset could suggest a dysfunction of the inhibitory control system on the trigeminal networks, which may predispose to migraine attacks.

Demographic characteristics and prognosis in a Flemish amyotrophic lateral sclerosis population.

Abstract: We describe the genetic and demographic characteristics of patients with amyotrophic lateral sclerosis (ALS) in Flanders, Belgium. Prognostic factors related to survival are examined. ALS was familial in 8.6% of all MND patients. In 6 of 8 apparently unrelated families, an SOD1 mutation was found. In sporadic ALS, mean age at onset was 57.1 years. There was a male preponderance (1.2:1) and the disease had a bulbar onset in 19%. Median survival was 32 months (95% CI 26-46). The presence of an APOE-epsilon 4 allele was not associated with a bulbar onset of ALS, an earlier age at onset or a shorter median survival. Variables examined in a multivariate analysis included age, sex, site of onset, delay from onset to diagnosis, and % forced vital capacity. Shorter survival was independently associated with higher age, bulbar onset, a short diagnostic delay, and a lower percent-predicted vital capacity at study entry. Simple clinical baseline characteristics can assist the clinician in estimating prognosis in ALS. The demographic characteristics of the Flemish ALS population do not seem to differ from those described in other parts of the world.

Dysferlin and muscular dystrophy.

Abstract: The limb-girdle muscular dystrophies are a highly heterogeneous group of muscle disorders with many different genetic causes now known. Amongst the causes of LGMD, the dysferlin gene stands out as novel for several reasons. It is the first known example of a C2 domain containing protein involved in a muscular dystrophy, mutations in the gene can be involved in a variable phenotype, and a naturally occurring mouse model for dysferlin deficiency has recently been identified. This article reviews the progress made in understanding this form of limb-girdle muscular dystrophy to date.

The usefulness of EEG, exogenous evoked potentials, and cognitive evoked potentials in the acute stage of post-anoxic and post-traumatic coma.

Abstract: Three-modality evoked potentials (TMEPs) have been used for several years in association with the EEG as a diagnostic and prognostic tool in acute anoxic or traumatic coma. Cognitive EPs have been recently introduced. EEG and cognitive EPs provide functional assessment of the cerebral cortex. TMEP parameters can be described by two indices: the index of global cortical function (IGCF) and the index of brainstem conduction (IBSC). Although it remains a unique tool for epilepsy assessment, the value of EEG is largely limited by its high sensitivity to the electrical environmental noise, its dependence on sedative drugs, and its inability to test the brainstem. Major TMEP alterations (absence of cortical activities more than 24 hours after the onset of post-anoxic coma, major pontine involvement in head trauma) are associated in all cases with an ominous prognosis (death or vegetative state). However, even if mild TMEP changes are associated with a good prognosis in 65% (post-anoxic coma) to 90% (head trauma) of cases, some patients never recover despite exogenous TMEPs that are only mildly altered in the acute stage. Thus, cognitive EPs can usefully complement exogenous EPs as a prognostic tool in coma. Indeed, even if the absence of cognitive EPs in comatose patients does not have any prognostic value, their presence implies a very high (more than 90%) probability of consciousness recovery. The major technical challenge for the future will be the development of reliable tools for continuous EEG and TMEP monitoring.

A case of Adams-Oliver syndrome associated with acrania, microcephaly, hemiplegia, epilepsy, and mental retardation

Abstract: Adams-Oliver syndrome (AOS) is a rare congenital disorder, characterized by aplasia cutis congenita (ACC) of the scalp and variable degrees of terminal transverse limb defects. In this article, a newborn infant diagnosed as AOS for a large scalp defect, acrania, and finger malformations is presented. The patient was hospitalized and the scalp defect was successfully repaired with several surgical operations. During the hospitalization septicemia, meningitis, and convulsions developed, but they were successfully treated with appropriate antibiotics, antifungal, and anticonvulsive agents, He was discharged five months after admission to the hospital. Now, he is 3 years old, and has microcephaly, moderate mental retardation, left spastic hemiplegia, and epilepsy.

Therapeutic coma or neuroprotection by anaesthetics

Abstract: Some surgical patients are at an increased risk for developing cerebral ischaemia. A subset of these patients is believed to benefit from putative cerebroprotective effects of anaesthetic agents. Therefore, in this setting these drugs could have therapeutic modalities, besides their auxiliary functions to make surgery possible. However, both animal and especially human data are very disappointing. Only the barbiturates and isoflurane have an experimental record warranting further research to delineate proper indications for their use as neuroprotective agents in surgical patients.

Adult-onset nemaline myopathy and monoclonal gammopathy: a case report.

Abstract: A 47-year-old female developed proximal limb weakness after hysterectomy for uterine fibromatosis. Muscle strength slowly improved, but relapse occurred at age 52. She presented with progressive gait difficulty, proximal limb weakness, and painful calves. Family history was not contributory. Cranial nerves, deep tendon reflexes, and sensation were normal. Serum creatine kinase was normal. An IgG kappa monoclonal protein was found. Nerve conduction studies were normal, but EMG showed brief small polyphasic motor unit action potentials with early recruitment in proximal muscles. Muscle biopsy showed abundant rods, atrophic muscle fibres, and type 1 fibre predominance. The sarcolemma was immunoreactive for IgG kappa. Plasmapheresis was unsuccessful, but methylprednisolone and azathioprine led to moderate improvement of muscle strength, associated with reduced monoclonal protein levels. This is the third case report, describing the association of monoclonal gammopathy and late-onset nemaline myopathy. Presence of a monoclonal protein at the sarcolemma and responsiveness to immunosuppressive treatment are suggestive of a dys-immune origin.

Isolated nuclear oculomotor nerve syndrome due to mesencephalic hematoma.

Abstract: Unilateral third nerve palsy with bilateral superior rectus paresis and bilateral ptosis is a typical condition for nuclear oculomotor nerve syndrome. We report a case of nuclear oculomotor nerve syndrome due to midbrain hemorrhage, as a rare cause. A 73-year-old man presented with an abrupt onset of double vision and difficulty opening his eyes. He had uncontrolled hypertension in his history. Neurological examination revealed right oculomotor palsy with impairment of bilateral upward gaze and bilateral ptosis. MRI showed a mesencephalic area of increased T1 signal and decreased T2 signal consistent with a subacute hematoma. It is emphasized that isolated mesencephalic hemorrhage may be the cause of the nuclear oculomotor nerve syndrome without associated neurological signs.

Isolated sixth nerve palsy from pontine infarct.

Abstract: Isolated sixth nerve palsy associated with pontine infarct is very rare due to close anatomic organization of the structures. A 62-year-old woman, who complained of diplopia, had a diagnosis of sixth nerve palsy. Ophthalmological examination revealed 30 PD left esotropia in primary position with limited abduction of the left eye. Neurologic examination was normal. MR showed a lacunar infarct in the pons consistent with a fascicular lesion. Cerebral angiography was normal. Pontine infarcts causing fascicular lesions should be kept in mind in isolated sixth nerve palsies.

Isolated bilateral abducens nerve palsy in primary sphenoidal sinus non-Hodgkin lymphoma.

Abstract: Isolated bilateral abducens nerve palsy is a rare complication of intracavernous tumors. A middle-aged man complaining of chronic horizontal diplopia was found to have bilateral abducens palsy as an initial manifestation of a massive non-Hodgkin lymphoma, originating from the sphenoidal sinus. This case is unique in two respects : the initial clinical presentation of isolated bilateral abducens involvement and the nature of the tumor, since only two cases of sphenoidal sinus lymphoma have been reported.

An attempt of gene therapy in Duchenne muscular dystrophy : overexpression of utrophin in transgenic mdx mice

Abstract: Dystrophin, its functions and the consequences of its absence are briefly reviewed. The animal model of Duchenne myopathy, the mdx mouse, was used to over-express utrophin by transgenesis technology. A battery of functional tests, including mechanical responses (force development and resistance to imposed stretch), intracellular calcium homeostasis and metabolic reaction to muscle activity were applied to check the functional recovery obtained by over-expression of utrophin. For most parameters tested, recovery amounted to 80%, demonstrating that utrophin can very efficiently act as a surrogate for dystrophin.

Mechanisms of functional restoration after brain injury.

Abstract: The mechanisms accounting for clinical improvement after brain injury are still a matter of debate. Better knowledge of the recovery process is important for it might be influenced by therapy. This article reviews a number of studies devoted to the physiopathology of recovery from aphasia and visuo-spatial neglect after the acute stage, using various methods (cerebral blood flow and metabolism measurements, dichotic listening, transcranial Doppler ultrasonography, functional magnetic resonance imaging) with special reference to the contribution of methods using activation procedures.

Mitochondrial cytopathies and neuromuscular disorders.

Abstract: In the last decade, mitochondrial diseases were shown not to be rare but to represent an important group of metabolic disorders. Defects are caused by mutations either located in nuclear genes or in mitochondrial genes. Nuclear gene defects are found in complex IV deficient and complex I deficient patients. Deficiencies of complex II are extremely rare. Different phenotypes are associated with complex IV deficiency, including a neonatal form, cardio-encephalomyopathy in young infants, Leigh syndrome, and pure myopathy. Mutations can be found in the complex IV assembly genes, such as the SURF-1 gene and the SCO2 gene. Different phenotypes are also found in complex I deficient patients and include a neonatal form, Leigh syndrome, pure myopathy, pure cardiomyopathy or multiple-system involvement. In some disorders, the mitochondrial DNA abnormalities are caused by a nuclear gene defect (Alpers-Huttenlocher syndrome, autosomal dominant multiple mitochondrial DNA deletion syndrome, and MNGIE syndrome). Since 1988, more then 70 different mutations were reported in the mitochondrial DNA. Some point mutations are associated with a specific phenotype, others have a wide range of clinical symptoms. We expect that many more mitochondrial DNA mutations will be identified in the future. The number of mutations in nuclear genes will also increase, especially since progress has been made in techniques used for identification of nuclear genes (microcell transfer).

Nerve biopsy: indications and contribution to the diagnosis of peripheral neuropathy. The experience of the Born Bunge Foundation University of Antwerp and University of Liege between 1987 and 1997.

Abstract: We reviewed 355 nerve biopsies analysed at the Laboratories of Neuropathology of the Born-Bunge Foundation/University of Antwerp (BBF/UIA) and University of Liege (ULg) between 1987 and 1997. We examined the indications for nerve biopsy, the yield of the procedure, and the influence of clinical and neuropathological parameters. Contributory biopsies accounted for 35.5% and 47.3% respectively at ULg and BBF/UIA laboratories: of these, one third showed specific histological findings, the majority being informative only when combined with the relevant clinical data. The profile of indications for nerve biopsy was roughly comparable in both laboratories. The search for an inflammatory neuropathy prompted 35-40% of all biopsies with more than 50% of specimens being informative in this indication. The lowest yield (20%) was obtained among the nerve biopsies performed in the absence of any presumptive aetiology. These accounted for 22-33% of all cases. Inadequate surgical resection, delays in transport or processing errors precluded histological study of 4% (BBF/UIA) to 8% (ULg) of the specimens. We conclude that nerve biopsies should be performed by experienced surgeons and handled in specialised laboratories. Only a relatively small number of causes of neuropathy can be diagnosed on the basis of histology alone. More often, contributory biopsies will result from the combination of non-specific suggestive histological features with relevant clinical information. The diagnostic yield of nerve biopsy is function of careful patient selection and close collaboration between the clinician and the neuropathologist.

Electrodiagnosis of demyelinating neuropathies

Abstract: The inflammatory demyelinating neuropathies constitute a significant proportion of the acquired polyneuropathies. Major progress in finding the causes and in the treatment of these neuropathies has been made over the last decade. Early recognition is of paramount importance, because timely and appropriate treatment can largely reduce morbidity and disability. Electrodiagnosis plays a key role in the detection and characterization of the inflammatory demyelinating neuropathies. Electrodiagnostic criteria for primary demyelination have therefore been developed. They are empirically based on changes of nerve conduction parameters in populations of patients with a confirmed clinical and laboratory diagnosis of inflammatory demyelinating neuropathy. The challenge consists of defining criteria sets that are highly specific but also as sensitive as possible. Most of the hereditary demyelinating neuropathies are part of Charcot-Marie-Tooth disease type 1. The pattern of nerve conduction abnormalities usually provides valuable clues for the distinction from chronic inflammatory demyelinating neuropathies.

Comparison of fluorine-18 deoxyglucose and O-15 water PET in temporal lobe epilepsy.

Abstract: This study reports a comparison of Fluorine-18 deoxyglucose positron emission tomography (FDG-PET) and O-15 water (H2(15)O) PET with regard to lateralization of the seizure focus in patients with complex partial epilepsy. The analysis of 35 patients who had an anterior temporal lobectomy for medically intractable seizures indicated that FDG- and H2(15)O-PET were highly correlated in demonstrating the epileptic focus. FDG- and H2(15)O-PET showed significant asymmetries in 83% and 77% of cases respectively. The lateralization with visual analysis of MRI was found to be lower than both FDG and blood flow imaging. Ictal electroencephalography (EEG) lateralizations were concordant with sites of blood flow and FDG-PET abnormalities. Thirty-three patients (94%) were seizure-free or improved significantly after surgery. In conclusion, blood flow PET yielded similar results compared to FDG-PET and can be a valuable modality in preoperative evaluation of patients with temporal lobe epilepsy.

Thalamic hand dystonia: an MRI anatomoclinical study.

Abstract: Focal dystonia has been attributed to lesions involving the basal ganglia and/or thalamus. Hand dystonia was studied in a patient with a unilateral thalamic infarction documented by MRI. A 18-year-old girl presented with severe isolated dystonia of the right hand as a sequel of perinatal infarction. MRI scan revealed infarction affecting part of the dorsomedian, lateral posterior, ventral lateral, ventral posterior lateral nuclei, and centromedian-parafascicular nucleus of the contralateral thalamus. The unique MRI anatomoclinical presentation of this case, taken together with the literature data, could provide evidence that a lesion affecting one or several thalamic nuclei, including the centromedian nucleus, can induce hand dystonia.

Neuropraxia of the cervical spinal cord following cervical spinal cord trauma: a report of five patients.

Abstract: Neuropraxia of the cervical spinal cord is a rare condition which is almost exclusively reported in American football players following cervical hyperextension or hyperflexion trauma. In this entity-neurological symptoms of both arms and legs for a period of up to 15 minutes are observed with complete recovery. We report the characteristics of five patients not involved in contact sport activities with a neuropraxia of the spinal cord following cervical trauma. In four of the five patients, this syndrome was associated with a cervical canal stenosis. Surgical decompression was performed in two patients with progressive neurological symptoms after an initial period of recovery. The cases illustrates that although neuropraxia of the spinal cord is usually seen in athletes, also other persons may be at risk for developing this condition, especially when a preexisting spinal stenosis is present. Patients who experienced neuropraxia of the spinal cord should thus be evaluated carefully for the presence of cervical spinal cord abnormalities.

A "cortico-basal degeneration"-like syndrome as first sign of progressive multifocal leukoencephalopathy.

Abstract: We report an unusual case of probable progressive multifocal leukoencephalopathy (PML), who initially presented with a right-sided movement disorder, including upper limb dystonia, tremor, and dyspraxia, reminiscent of corticobasal degeneration. In the further course, the patient developed disorientation, confusion, and bradyphrenia. The appearance of white matter MRI lesions as well as a positive PCR test result for JC-virus in the cerebrospinal fluid finally led to the correct diagnosis.

The potential and limitations of transcranial Doppler in clinical practice

Abstract: The aim of this review is to bring the clinical relevance of transcranial Doppler (TCD) to light with all of its possibilities and limitations. Indeed TCD, a non-invasive ultrasound technique, allows instantaneous evaluation of the cerebral blood flow: adding physiological information to the anatomical images. Although TCD is frequently used in some places, in other regions TCD remains relatively unknown. However TCD can help the neurologist not only in the management of cerebrovascular disease, but also in a wide variety of central nervous system disorders. TCD monitoring with multichannel and multigate probes can assess vascular reactivity by following various parameters, such as CO2 or arterial blood pressure. Despite the need for more work, emboli detection seems to offer great potential in the future diagnosis, treatment and prevention of stroke.

Usefulness of gait analysis combined with motor point block in a stroke patient.

Abstract: This clinical note describes a typical case of dynamic varus deformity of the rear foot in a stroke patient. An overactive Tibialis Posterior muscle seemed mainly responsible for the varus deformity. However, this hypothesis was not confirmed by a motor point block of this muscle. It appeared that the Tibialis Posterior and Extensor Hallucis Longus muscles were both involved in the varus deformity. A double motor point block of both the Tibialis Posterior and Extensor Hallucis Longus muscles was performed. Kinematic and kinetic data showed improvement. This case report illustrates the usefulness of gait analysis combined with motor point block in the diagnosis and management of gait disturbance.

Molecular genetics of inherited peripheral neuropathies: who are the actors?

Abstract: Charcot-Marie-Tooth disease, the most common variant of the inherited peripheral neuropathies, has a prevalence of 1/2500. Clinical, electrophysiological, neuropathological and molecular genetic studies have demonstrated extensive heterogeneity. Currently, 30 genetic loci are known for distinct CMT types and related inherited peripheral neuropathies, while many other types have been excluded for linkage to these loci. Recent molecular genetic studies have demonstrated the involvement of 8 genes that encode proteins with very diverse functions. These include a structural protein confined to the compact myelin, a cytoskeletal protein, an adhesion molecule, a gap-junction protein, a transcription factor, a receptor for a neurotrophic factor, a phosphatase and a protein involved in signal transduction and cell cycle regulation.

Generation of isolated words in normal subjects

Abstract: This study aims at analyzing the performance according to age, sex, and educational level in 112 French normal subjects on word generation tests, i.e., time-limited production of a noun or a verb semantically linked to a target "noun" or "verb". The nature of hits (exclusively production of nouns) has moreover been analyzed according to different features of the targets: noun vs verb, names of natural objects vs handmade objects, transitive vs intransitive verbs. Results show 1) a significant effect of age and educational level on performance, 2) a degree of difficulty, the verb/verb production test being significantly more difficult than the three other tests, 3) a convergency effect according to the natural vs handmade dichotomy, as subjects tend to produce, without specific instruction, an item belonging to the same category as that of the stimulus, and 4) object nouns tend to be produced in response to transitive verbs whereas subject nouns are not predominantly produced in response to intransitive verbs.

Pathogenesis and treatment of inflammatory demyelinating polyradiculoneuropathy.

Abstract: Inflammatory demyelinating polyradiculoneuropathy causes a spectrum of conditions ranging from acute (Guillain-Barre syndrome), through subacute to chronic forms. The pathogenesis of acute forms is related to antibody responses against glycolipid epitopes which mimic bacterial, especially Campylobacter jejuni, structures but T cells are also involved. The pathogenesis of chronic forms is poorly understood. Different forms differ in their responses to steroids. Chronic inflammatory demyelinating polyradiculoneuropathy responds to steroids but a variant multifocal motor neuropathy and the acute forms of inflammatory demyelinating polyradiculoneuropathy do not. Acute and chronic forms respond to plasma exchange and intravenous immunoglobulin.