Vagus nerve stimulation for intractable epilepsy: a review

Electrical stimulation of the vagus nerve in the neck by using a programmable stimulator similar to a cardiac pacemaker is being explored as a treatment for epilepsy. There is sound rationale based on studies of animal seizure models for pursuing this treatment modality, and early clinical trials provide support for efficacy in patients with intractable epilepsy at least equivalent to that of some of the new antiepileptic drugs. Safety and tolerability have been demonstrated in >800 patients worldwide since the first implant in 1988. Most of these had partial seizures for which resective epilepsy surgery was not feasible or had failed, but efficacy of vagal stimulation appears to be the same for both partial and generalized epilepsy. Specific selection criteria for this procedure have yet to be established, and further studies are warranted to determine whether vagal stimulation becomes an accepted procedure for epilepsy management.     

Vagus nerve stimulator as a treatment for intractable epilepsy

Vagus nerve stimulation was recently approved for control of medically intractable seizures. This therapy provides some relief of seizures for selective patients, however seizure freedom using this device is uncommon. Vagus nerve stimulation appears to work by calming "hyperexcited" nerve cells and reverting brain activity to its normal patterns. Many people do have significant relief in the intensity and duration of their seizures and report improved quality of life using this device.     

Combination vigabatrin and lamotrigine therapy for intractable epilepsy

OBJECTIVE: To determine whether interleukin (IL)-10, besides its potent anti-inflammatory properties, causes depression of splenocyte functions in a murine model of gram-negative endotoxemia. DESIGN: Mice (strain C3H/HeN) were injected intravenously with 1 mg of Escherichia coli lipopolysaccharide at 15 minutes after intravenous injection of either 200 U of recombinant murine IL-10 or saline solution. Serum levels of tumor necrosis factor alpha, IL-6, and IL-1 alpha were determined at 90 minutes and 12 hours after lipopolysaccharide challenge. In addition, splenocyte proliferation and lymphokine release (IL-2, IL-6, and interferon gamma) were measured. RESULTS: Pretreatment with IL-10 markedly reduced (P < .05) serum levels of tumor necrosis factor alpha (-79%), IL-6 (-94%), and IL-1 alpha (-69%), but it significantly inhibited splenocyte proliferation (-32%) and IL-2 (-40%), IL-6 (-49%), and interferon gamma (-54%) release of splenocytes. CONCLUSIONS: Interleukin-10 prevents E coli lipopolysaccharide-induced cytokinemia but dampens antigen-driven cellular immune responses. Although IL-10 protects against the detrimental effects of proinflammatory cytokines by deactivation of macrophages, its immunosuppressive effect may augment susceptibility to repeated or continuous invasion of microorganisms, as it is observed during clinical sepsis.     

MR imaging of Kallmann syndrome, a genetic disorder of neuronal migration affecting the olfactory and genital systems

PURPOSE: We report the MR findings in nine patients with clinical and laboratory evidence of Kallmann syndrome (KS), a genetic disorder of olfactory and gonadal development. In patients with KS, cells that normally express luteinizing hormone-releasing hormone fail to migrate from the medial olfactory placode along the terminalis nerves into the forebrain. In addition, failed neuronal migration from the lateral olfactory placode along the olfactory fila to the forebrain results in aplasia or hypoplasia of the olfactory bulbs and tracts. Patients with KS, therefore, suffer both reproductive and olfactory dysfunction. METHODS: Nine patients with KS underwent direct coronal MR of their olfactory regions in order to assess the olfactory sulci, bulbs, and tracts. A 10th patient had MR findings of KS, although the diagnosis is not yet confirmed by laboratory tests. RESULTS: Abnormalities of the olfactory system were identified in all patients. In particular, the anterior portions of the olfactory sulci were uniformly hypoplastic. The olfactory bulbs and tracts appeared hypoplastic or aplastic in all patients in whom the bulb/tract region was satisfactorily imaged. In two (possibly three) patients, prominent soft tissue in the region of the bulbs suggests radiographic evidence of neurons that have been arrested before migration. CONCLUSIONS: Previous investigators of patients with KS used axial MR images to demonstrate hypoplasia of the olfactory sulci but offered no assessment of the olfactory bulbs. In the present study we used coronal images to show hypoplasia of both olfactory sulci and bulbs. In addition, we found what we believe to be the radiologic correlate of arrested neuronal migration in KS.     

Targeted deletion of the PEX2 peroxisome assembly gene in mice provides a model for Zellweger syndrome, a human neuronal migration disorder

Zellweger syndrome is a peroxisomal biogenesis disorder that results in abnormal neuronal migration in the central nervous system and severe neurologic dysfunction. The pathogenesis of the multiple severe anomalies associated with the disorders of peroxisome biogenesis remains unknown. To study the relationship between lack of peroxisomal function and organ dysfunction, the PEX2 peroxisome assembly gene (formerly peroxisome assembly factor-1) was disrupted by gene targeting. Homozygous PEX2-deficient mice survive in utero but die several hours after birth. The mutant animals do not feed and are hypoactive and markedly hypotonic. The PEX2-deficient mice lack normal peroxisomes but do assemble empty peroxisome membrane ghosts. They display abnormal peroxisomal biochemical parameters, including accumulations of very long chain fatty acids in plasma and deficient erythrocyte plasmalogens. Abnormal lipid storage is evident in the adrenal cortex, with characteristic lamellar-lipid inclusions. In the central nervous system of newborn mutant mice there is disordered lamination in the cerebral cortex and an increased cell density in the underlying white matter, indicating an abnormality of neuronal migration. These findings demonstrate that mice with a PEX2 gene deletion have a peroxisomal disorder and provide an important model to study the role of peroxisomal function in the pathogenesis of this human disease.     

Periventricular nodular heterotopia and intractable temporal lobe epilepsy: poor outcome after temporal lobe resection

We describe 5 women and 5 men with periventricular nodular heterotopia and electroclinical features suggestive of temporal lobe epilepsy, who were surgically treated for control of medically refractory seizures. Magnetic resonance imaging revealed bilateral periventricular nodular heterotopia in 7 of the 10 patients. Because of the lack of clear localization, 6 patients were studied with intracranial depth electrode recordings. Seizures were of hippocampal onset (3 patients), regional temporal lobe onset (2 patients), or occipital-temporal onset (1 patient). Anterior temporal lobectomy was performed in 6 patients; selective amygdalohippocampectomy, in 1; and anterior temporal lobectomy plus resection of the heterotopic tissue, in 3. None of the 9 patients followed for more than 12 months postoperatively were seizure free. Two patients were initially seizure free for approximately 18 months, but then seizures recurred. One patient had a major reduction in seizure frequency at a 39-month follow-up after most of the unilateral heterotopic tissue was included in the temporal resection. Temporal resection did not lead to a long-term favorable outcome in this group of patients with periventricular nodular heterotopia and epileptogenic discharges involving the temporal lobe. This suggests a more widespread disorder with epileptogenic activity possibly originating in or near the heterotopic tissue. The clinical and electrographic features of periventricular nodular heterotopia pointing to temporal lobe origin are misleading and temporal resection does not result in long-term cessation of seizures.     

Localised carcinoma of the prostate: a paradigm of uncertainty

The incidence and prevalence of prostate cancer is increasing. A number of aetiological factors including age, race, family history and diet have been implicated. The majority of patients present with disease which is amenable only to palliation. Digital rectal examination, serum prostate-specific antigen and transrectal ultrasound can lead to a prostatic biopsy. Transrectal ultrasound, magnetic resonance imaging, bone scan and a chest X-ray are used for staging. The management of localised cancer is shrouded in uncertainty. Three options exist, watchful waiting, radiotherapy, and radical total prostatectomy. The published data are inadequate for a valid comparison of these, and none has been shown to offer an advantage. Surgery, and to a lesser degree radiotherapy, have a significant morbidity. It is hoped that through better understanding our management of this disease will improve.     

Psychometric properties and factor structure of the Wechsler Memory Scale-Revised in a sample of persons with intractable epilepsy

A family is reported with dentinal dysplasia type I affecting both dentitions. Presenting features included unusual mobility of the teeth, followed by early exfoliation; normal clinical shape of the crowns of the teeth, but with an amber color without any sign of attrition or abnormal loss of enamel. Radiographic findings showed pulp-chamber and root-canal obliteration, poor root formation, radiolucent linear appearance of the pulp chamber parallel to the cementoenamel junction and frequent periapical radiolucencies. Histological studies have reported large masses of calcified tubular dentin, atypical osteodentin, and also true denticle.     

A disorder of psychosexual identity in epilepsy and endocraniosis

Anaerobically grown bacteria isolated from the hindgut contents of the termites Coptotermes lacteus (Froggatt), Mastotermes darwiniensis Froggatt and Nasutitermes exitiosus (Hill) were nitrogenase-positive as assayed by acetylene reduction. Nitrogen fixation, confirmed with 15N2, was highest in the isolate from M. darwiniensis. All isolates were identified as Citrobacter freundii (Braak) Werkman & Gillen.     

Evidence of enhanced kindling and hippocampal neuronal injury in immature rats with neuronal migration disorders

To clarify the characteristic features of nosocomial pneumonia in a community hospital, we performed a clinical analysis of 147 patients (155 episodes) with nosocomial pneumonia. The following results were obtained. 1, Regarding the risk factors for nosocomial pneumonia, factors such as the patient whose age was over 65 years, a duration of admission of over one month, performance status 4 and underlying respiratory diseases associated with the appearance of nosocomial pneumonia. 2, The causative microorganism isolated from the sputum of the patient with nosocomial pneumonia was frequently a multi-drug resistant microorganism such as Methicillin-resistant Staphylococcus aureus (MRSA). 3, regarding treatment, although several antibiotics were administered for a long time, mechanical ventilation was used on 31% of the patients, and steroid pulse therapy was carried out on 24%. The clinical efficacy was poor with a 50% mortality rate. The reason why treatment of nosocomial pneumonia was difficult is thought to be been related to the general condition of these inpatients and to the appearance of a multi-drug resistant, polymicrobial microorganisms.     

Somatosensory evoked potentials with a unilateral migration disorder of the cerebrum

Transcranial electrical stimulation can be used for clinical investigations of the central nervous system and for monitoring of motor nerve tracts during surgical operations. We wished to reduce the pain involved with the transcranial electrical stimulation and to improve the usefulness of the method for monitoring during surgical operations. A dedicated transcranial electrical stimulator was designed having special features to reduce the pain sensation and the nerve blocking effect of anaesthetics. It provides constant current and constant voltage stimulation pulses with very short duration and high amplitude. The pulse length is adjustable in the range of 15 to 125 microseconds, while the maximum amplitude is 100 V and 1 A for voltage and current stimulation modes, respectively. Special features included high-repetition-rate pulse trains (50-2000 pulses s-1) and a three-electrode stimulation configuration. We suggest that the electrical transcranial stimulation has the potential to be a relatively painless method for routine clinical investigations and a reliable method for monitoring during surgery.     

A case of intractable temporal lobe epilepsy: discrepancy between epileptogenic area and structural lesion demonstrated by subdural recording

We reported a 25-year-old man with intractable right temporal lobe epilepsy in whom subdural recording successfully delineated the epileptogenic area in the right anterior mesial to basal temporal region in spite of the presence of a postoperative lesion in the right posterior temporal region. The patient underwent right posterior temporal resection due to ependymoma at the age of 8 years. Since age 19, he had suffered from medically intractable psychomotor seizures. Ictal scalp-recorded EEG suggested an epileptogenic area at the right temporal area, but it could not specifically demarcate the site because of bone deficits from the previous surgery. Ictal SPECT showed a hyperactive area in the right anterior temporal area, which was inconsistent with the MRI finding. In case of partial epilepsy associated with structural lesion like in the present case, if results of various non-invasive studies are discrepant as to the epileptogenic area, invasive studies using, for example, subdural EEG monitoring is necessary to determine the responsible area.     

Congenital muscular dystrophy, white-matter abnormalities, and neuronal migration disorders: the expanding concept

The congenital muscular dystrophies are a heterogeneous, recessively inherited group of disorders that have been subclassified on the basis of clinical central nervous system involvement. We report two children with "pure" congenital muscular dystrophy, one merosin negative and one merosin positive with extensive white matter and occipital cortical neuromigration abnormalities on magnetic resonance imaging (MRI). The first patient (merosin-negative congenital muscular dystrophy) presented with hypotonia and weakness in the neonatal period and subsequently was found to have a leukoencephalopathy and occipital cortical dysplasia on magnetic resonance imaging. The second patient presented with developmental delay without definite weakness. Initial investigations revealed a leukoencephalopathy and cortical dysplasia, but the patient subsequently was shown to have merosin-positive congenital muscular dystrophy. These patients illustrate that white-matter changes are not specific for merosin-negative congenital muscular dystrophy alone and that extensive cortical abnormality can be found in both groups of patients. In addition, our second patient illustrates a nonmuscular mode of congenital muscular dystrophy presentation that should be considered in patients with a "nonprogressive leukodystrophy."     

Identification of Caenorhabditis elegans genes required for neuronal differentiation and migration

To understand the mechanisms that guide migrating cells, we have been studying the embryonic migrations of the C. elegans canal-associated neurons (CANs). Here, we describe two screens used to identify genes involved in CAN migration. First, we screened for mutants that died as clear larvae (Clr) or had withered tails (Wit), phenotypes displayed by animals lacking normal CAN function. Second, we screened directly for mutants with missing or misplaced CANs. We isolated and characterized 30 mutants that defined 14 genes necessary for CAN migration. We found that one of the genes, ceh-10, specifies CAN fate. ceh-10 had been defined molecularly as encoding a homeodomain protein expressed in the CANs. Mutations that reduce ceh-10 function result in Wit animals with CANs that are partially defective in their migrations. Mutations that eliminate ceh-10 function result in Clr animals with CANs that fail to migrate or express CEH-23, a CAN differentiation marker. Null mutants also fail to express CEH-10, suggesting that CEH-10 regulates its own expression. Finally, we found that ceh-10 is necessary for the differentiation of AIY and RMED, two additional cells that express CEH-10.     

Cysticercosis and epilepsy: a critical review

Neurocysticercosis (NC) remains a major public health problem in developing and some developed countries. Currently, the best procedures for diagnosing NC are neuroimaging studies. Immunoserologic assays, such as enzyme-linked immunoelectrotransfer blot assay (EITB) or enzyme-linked immunosorbent assay (ELISA), detect antibodies against Taenia solium, or cysticercus. Consequently, they are useful in identifying a population at risk of contact with the parasite but do not necessarily indicate a systemic active infection. Most seropositive individuals are asymptomatic. No data from prospective studies concern the proportion of these individuals that will develop seizures or other neurologic symptoms. There is a discrepancy between the results of serologic assays and neuroimaging studies: >50% of those individuals with NC diagnosed by computed tomography (CT) scan test EITB negative. Pathophysiologic classification of NC into active, transitional, and inactive forms permits a good correlation between clinical manifestations and neuroimaging procedures and facilitates medical and surgical management and research. The most frequent clinical manifestations of NC are seizures. We assume that NC is the main cause of symptomatic epilepsy in developing countries; however, no case-control or cohort studies demonstrate this association. Most patients with NC with seizures have a good prognosis; nevertheless, further studies analyzing factors related to recurrence of seizures and possibilities of discontinuation of antiepileptic medications (AEDs) are needed. Regarding treatment of NC with antihelminthic drugs, no controlled clinical trials exist that establish specific indications, definitive doses, and duration of treatment. The most effective approach to taeniasis/cysticercosis infection is prevention. This should be a primary public health focus for developing countries. We critically review the available information regarding the epidemiology and diagnosis of human cysticercosis, the physiopathology and imaging correlation of the parasite in the central nervous system (CNS) of the host, the relation between seizures or epilepsy and NC, and the issues surrounding the treatment and prognosis of NC, including the use of antihelminthic therapy.