Gait instability in valproate-treated patients: Call to measure ammonia levels.

OBJECTIVE: Hyperammonemia induced by valproate (VPA) treatment may lead to several neurological and systemic symptoms as well as to seizure exacerbation. Gait instability and recurrent falls are rarely mentioned as symptoms, especially not as predominant ones. METHODS: We report five adult patients with frontal lobe epilepsy (FLE) who were treated with VPA and in whom a primary adverse effect was unstable gait and falls. RESULTS: There were four males and one female patients with FLE, 25-42-year-old, three following epilepsy surgery. All of them were treated with antiepileptic drug polytherapy. Gait instability with falls was one of the principal sequelae of the treatment. Patients also exhibited mild encephalopathy (all patients) and flapping tremor (three patients) that developed following the addition of VPA (three patients) and with chronic VPA treatment (two patients). VPA levels were within the reference range. Serum ammonia levels were significantly elevated (291-407 µmole/L, normal 20-85) with normal or slightly elevated liver enzymes. VPA dose reduction or discontinuation led to the return of ammonia levels to normal and resolution of the clinical symptoms, including seizures, which disappeared in two patients and either decreased in frequency or became shorter in duration in the other three. CONCLUSIONS: Gait instability due to hyperammonemia and VPA treatment is probably under-recognized in many patients. It can develop when the VPA levels are within the reference range and with normal or slightly elevated liver enzymes.

Psychogenic seizures: long-term outcome in patients with and without epilepsy.

OBJECTIVES: Psychogenic non-epileptic seizures (PNES) may resemble epileptic events. Epileptic and non-epileptic seizures are not mutually exclusive phenomena and may coexist in the same patient. The aim of this study was to evaluate the long-term outcome of psychogenic events in patients with PNES alone and those with both PNES and epilepsy (PNES + EPI) as diagnosed by video-EEG (vEEG) monitoring. MATERIALS AND METHODS: All adult admissions to the Tel-Aviv Medical Center's vEEG unit between 2004 and 2009 were screened for the presence of PNES. We retrospectively retrieved data from their medical files and supplemented the follow-up by a telephonic questionnaire. RESULTS: Eligible patients (n = 51) were divided into those with PNES + EPI (n = 24) and those with PNES alone (n = 27). The follow-up period was 4.8 ± 0.3 and 4.3 ± 0.3 years, respectively. Both groups had similar female predominance and similar age at admission to the vEEG unit. Time from PNES onset to hospitalization was longer in PNES patients compared to those with PNES + EPI. The majority of subjects in each group reported a history of at least one major stressful life event. Opisthotonus was significantly more frequently observed in PNES patients, and they had more events during vEEG hospitalization. Psychogenic events ceased during the follow-up period in 22% of the PNES patients and in 58% of the PNES + EPI patients (P > 0.001). CONCLUSION: Our results indicate that following vEEG-based diagnosis of PNES, the long-term outcome of PNES cessation may be more favorable for patients with concomitant epilepsy than for patients without epilepsy.

The prognosis of refractory epilepsy patients rejected from epilepsy surgery.

OBJECTIVE: Up to one-third of individuals diagnosed as having epilepsy continue to have seizures despite appropriate anti-epileptic drug treatment. These patients are often referred for presurgical evaluation, and many are rejected from focal resective surgery due to medical reasons or, alternatively, they choose not to undergo it. We compared the outcomes and characteristics of the non-operated patients who continued on medical therapy alone with those who underwent vagus nerve stimulator (VNS) implantation in addition to medical therapy. METHODS: The medical records of consecutive adult patients referred for presurgical evaluation for suitability for epilepsy surgery in the Tel-Aviv Sourasky Medical Center between 2007 and 2011 and were rejected from or decided against surgery were reviewed. Updated information on seizure frequency was supplemented by telephone interviews between April and July, 2013. RESULTS: Fifty-two patients who continued solely on medical therapy and 35 patients who additionally underwent VNS implantation were included in the study. Forty-seven of the former and 33 of the latter agreed to be interviewed. There was a significant improvement in the seizure frequency between the time of the presurgical evaluation and the time of the interview in both groups. Eight medically treated patients (17%) and 2 patients who also underwent VNS implantation (6%) reported being seizure-free during the preceding 3 months. CONCLUSIONS: A considerable minority of patients with refractory epilepsy who were rejected or chose not to undergo epilepsy surgery may improve over time and even become seizure-free following adjustment of anti-epileptic drugs with or without concomitant VNS.

Utility of hospitalization following a first unprovoked seizure.

OBJECTIVES: Hospital admission in otherwise healthy patients following a first unprovoked seizure is controversial. We aimed to evaluate the influence of admission in a neurology department on the identification of risk factors for seizure recurrence in patients with a first unprovoked seizure. MATERIALS AND METHODS: We retrospectively reviewed the medical records of patients with a first unprovoked seizure, who were admitted to the neurology departments at two medical centers between 2007 and 2009. Risk factors for seizure recurrence included the following: abnormal neurological examination, abnormal brain CT scan, and epileptiform discharges on the EEG. RESULTS: The study group included 97 patients (52 men) aged 18-85 years (mean 42). Eighty-seven (90%) patients were admitted following a generalized tonic-clonic seizure. Risk factors were identified in the emergency room (ER) in 36 (37%) patients, mainly including abnormalities of the neurological examination and brain CT scan. Nineteen (20%) patients had a risk factor which was not apparent during ER evaluation, consisting of epileptiform activity on the EEG. Five (5%) patients had recurrent seizures during admission, three of them without risk factors during the ER evaluation. CONCLUSIONS: Risk factors for seizure recurrence were detected during admission in nearly a quarter of the patients who presented to the emergency room with a first unprovoked seizure. Because the main advantage of admission is the EEG recording, we suggest that an early EEG should be obtained in these patients either during admission or through a special accelerated outpatient arrangement.

A revised intracarotid etomidate memory (Wada) procedure.

OBJECTIVES: To evaluate unilateral memory function by the means of a modified Montreal etomidate speech and memory procedure (e-SAM) in epilepsy patients who were candidates for standard anterior temporal lobectomy involving resection of mesial temporal lobe structures. MATERIALS AND METHODS: After the first three patients experienced significant side effects with the e-SAM procedure, we modified the procedure to a single bolus injection. The neuropsychological data of all 21 patients who underwent unilateral memory testing by means of intracarotid injection of etomidate were analyzed. RESULTS: There was a significant difference in memory scores when injections were on the side ipsilateral to the epileptogenic focus compared with when the injections were on the contralateral side (P < 0.01), supposedly reflecting unilateral hippocampal memory function and dysfunction. In addition, the procedural modification resulted in eradication of all major side effects in the ensuing 18 patients. CONCLUSIONS: The technical modification of the Montreal procedure from continuous to bolus injection effectively enabled the demonstration of the relative weakness of the memory function of the epileptogenic hemisphere. The revised etomidate procedure provided the clinical information on unilateral hippocampal memory function necessary for surgical decision.

Postponing the morning dose of AEDs: effect on the epileptiform EEG activity.

BACKGROUND: The effects of postponing the morning dose of antiepileptic drugs (AEDs) before undergoing an electroencephalogram (EEG) on the likelihood of recording interictal epileptiform activity (IEA) in patients with epilepsy are unclear. METHODS: This was a prospective study on patients undergoing video-EEG monitoring. The 3-h recordings used for evaluation started at 08:00 am. Each subject received the usual AED dosage at 08:00 am on the first full day of recording but not until 11:00 am on the following day. IEA (spikes, sharp waves, and spike and wave complexes) was counted at 1-h intervals on each day and compared. Each subject served as his/her own control. The measureable serum drug levels were obtained at 10:00 am on both days. RESULTS: Fifty patients (age 32 ± 11.7 years, 22 women) were enrolled. Forty-seven had focal epilepsy, and three had generalized epilepsy. Six were on monotherapy, and 44 were on polytherapy. The number of IEAs w/wo medication was similar throughout each hour. Twenty-five patients had IEA on the 1st day, and 28 had IEA on the 2nd day. Twenty-one had IEA on both days, while 18 had none on either day. Seven of the 25 without IEA on the 1st day had IEA on the 2nd day, and 4 of the 25 with IEA had no IEA on the 2nd day. Age, gender, epilepsy type, disease duration, seizure frequency, and AED type did not influence IEA. CONCLUSIONS: Delaying the morning dose of AEDs prior to an EEG tracing was not associated with increased IEA in patients with epilepsy.

Possible remote functional reorganization in left temporal lobe epilepsy.

OBJECTIVE: To provide functional magnetic resonance imaging-based insight into the impact of left temporal lobe epilepsy (TLE) on language-related functional re-organization. MATERIALS AND METHODS: Ten right-handed patients with left TLE were compared with 10 matched healthy controls. Regional brain activation during the language task was measured in the inferior frontal gyrus (IFG) and in the superior temporal gyrus (STG), and the regional inter-hemispheric lateralization index (LI) was calculated. RESULTS: Left language lateralization was documented in all the patients and controls. Reduced lateralization in the IFG was due to decreased activity in the left frontal region rather than to increased activity in the right frontal region. The LI values in the STG correlated with the LI values in the IFG in the controls but not in the patients. CONCLUSIONS: The left IFG was most probably involved in the epileptogenesis and concomitant language-related cortical plasticity in patients with left TLE.

Long-term tetrahydroaminoacridine treatment and quantitative EEG in Alzheimer's disease.

The development of therapies for Alzheimer's disease (AD) has focused on drugs designed to correct the loss of cholinergic function within the central nervous system. Quantitative EEG (qEEG) changes associated with AD consist of background slowing. One way to study the effects of cholinergic drugs may be through assessment of their qEEG effects. The aim of the current work was to evaluate the effect of long-term treatment with tetrahydroaminoacridine (THA) on qEEG in AD patients.

Localized EEG abnormalities in acute carbon monoxide poisoning.

The EEG of a patient with acute carbon monoxide poisoning was characterized by lateralized sharp waves and a focal electrographic seizure discharge within hours of the exposure. These findings were associated with coma and focal motor seizures. The patient made a full clinical recovery, and the EEG was normal two months after the exposure. The association of a primarily diffuse cerebral insult after CO poisoning, with prominent lateralized epileptiform discharges in the EEG, is a distinctly unusual phenomenon.

Periodic triphasic waves in levodopa-induced encephalopathy.

Four patients with idiopathic Parkinson's disease developed subacute confusional states, associated with delusions, hallucinations, and myoclonus, following an increase in the dose of levodopa. The EEG revealed periodic generalized triphasic waves. The clinical condition and EEG cleared following levodopa dose reduction or discontinuation. This is the first report of encephalopathy associated with periodic triphasic activity following levodopa treatment.

Coma with triphasic wave pattern in EEG as a complication of temporal arteritis.

Coma is rare in temporal arteritis (TA). We describe a patient with TA who suddenly developed coma with a triphasic EEG pattern that resolved after initiation of steroid treatment. Although the arterial lesions in TA are segmental in nature, TA may present with signs of diffuse neurologic deficit; early treatment can result in complete resolution.

Routine and quantitative EEG analysis in Gilles de la Tourette's syndrome.

Gilles de la Tourette's syndrome (GdlT) is a neurobehavioral disorder, with a reportedly high frequency of EEG abnormalities. We performed EEGs on 48 consecutive patients with GdlT, and frequency analysis in 26 patients (17 males), and compared the results with those from age- and sex-matched normal controls. Routine 18-channel EEG revealed minimal diffuse nonspecific slowing in only 3 of 48 patients (6%) and in 2 of 26 controls (7.7%). The frequency analysis of the EEG of the 26 GdlT patients and their normal controls showed similar brain activity. We conclude that no significant differences exist between the EEG activity in GdlT patients as compared with that in sex- and age-matched controls in routine as well as in quantitative EEG.

Low-dose clozapine in the treatment of levodopa-induced mental disturbances in Parkinson's disease.

Delusions and other manifestations of psychotic behavior are common side effects in Parkinson's disease (PD) patients chronically treated with dopaminergic drugs. Clozapine, a dibenzodiazepine derivative, is an antipsychotic drug largely devoid of extrapyramidal side effects. We evaluated the effects of low doses of clozapine on the mental and motor functions in PD patients requiring antipsychotic treatment. Twenty-seven PD patients taking dopaminergic drugs and who had psychotic behavior received clozapine at 12.5 to 75 mg/d. Fifteen patients received clozapine for 1 to 11 months (mean, 6.8 months) and seven received it for 12 to 24 months (mean, 18 months). No patient exhibited motor deterioration, and the psychotic features disappeared immediately, allowing discontinuation of clozapine after several months in 10 patients. Fifteen patients are still receiving clozapine and are free of psychiatric symptoms. The clozapine treatment was discontinued after 5 days (25 mg/d) in two patients because of somnolence. No patient developed neutropenia. Clozapine in low doses is effective in the treatment of drug-induced delusions and hallucinations in PD.

Unverricht-Lundborg disease in a five-generation Arab family: instability of dodecamer repeats.

BACKGROUND: Unverricht-Lundborg disease (ULD) is the prototypical form of progressive myoclonus epilepsy, and subjects are usually very photosensitive. ULD is caused by mutations in the cystatin B (CSTB) gene; the most common mutation is expansion of a dodecamer repeat near the promoter. The authors studied a five-generation Arab family with ULD lacking photosensitivity. METHODS: An Arab family from the Galilee region of Israel with progressive myoclonus epilepsy was clinically evaluated. Blood samples were obtained from three living affected and 16 unaffected individuals. Expansion of dodecamer repeat in the CSTB gene was examined. RESULTS: The three living affected individuals showed spontaneous and action myoclonus, ataxia, and mild dementia. EEG in two individuals showed generalized polyspike-wave without photosensitivity. The family structure with large sibships and multiple consanguineous loops allowed the authors to examine the gene over four generations of adults. The three living affected individuals were homozygous for repeat expansions and 11 of the 16 unaffected family members were heterozygous. Instability was demonstrated by the presence of expansions of different sizes occurring on the same haplotype background in this inbred family. Fragment size variations could be unequivocally detected in two sibships. The expansions were in the 49 to 54 dodecamer repeat range. Changes in one generation were small, 1 to 4 repeat units, consisting of either enlargements or contractions. CONCLUSIONS: Instability of the expanded dodecamer repeats in the cystatin B gene is frequent. Almost invariably, a small change is observed in parent-child transmission. The lack of photosensitivity in this family is unexplained.

Fatal insomnia in a case of familial Creutzfeldt-Jakob disease with the codon 200(Lys) mutation.

Fatal familial insomnia (FFI) has been exclusively associated with a pathogenic mutation at codon 178 in the PRNP gene coupled with methionine (Met) at codon 129. We now describe a subject with familial Creutzfeldt-Jakob disease, heterozygous for the pathogenic lysine (Lys) mutation at codon 200 and homozygous for Met at codon 129 of the PRNP gene, who was affected by severe insomnia. At autopsy the patient had significant involvement of the thalamus, as previously described in subjects affected by FFI with the codon 178 mutation. This case demonstrates the wide variability of the clinical expressions in patients with the codon 200 mutation, that may include insomnia and thalamic pathology.

EEG abnormalities in clozapine-treated schizophrenic patients.

A prospective study of EEG findings and occurrence of seizures in patients with refractory schizophrenia treated with clozapine has been conducted. Pretrial EEG and EEG under treatment at a fixed dose of clozapine 300 mg/day were performed. Fifteen patients entered the study, four patients were withdrawn because of side effects or poor compliance. EEG abnormalities appeared in seven of the 11 patients who completed the study (64%): generalized slowing in six of them and epileptic activity in two (one patient had both types of change). None of the patients developed clinical seizures. EEG abnormalities were more frequently observed in those with better clinical response to clozapine and/or shorter duration of disease, although these findings were not statistically significant. We conclude that EEG abnormalities occur frequently (64%) in schizophrenic patients who receive clozapine. However, the EEG changes do not necessarily predict the occurrence of convulsions.

Intermittent rhythmic delta activity (IRDA) morphology cannot distinguish between focal and diffuse brain disturbances.

IRDA (intermittent rhythmic delta activity) is an abnormal generalized EEG pattern that is not specific to any single etiology and can occur with diffuse or focal cerebral disturbances. To determine whether different electrographic features of IRDA and associated EEG findings can differentiate underlying focal from diffuse brain disturbances, we performed a blind analysis of 58 consecutive EEGs with an IRDA pattern, recorded from 1993 until 1996, in which we evaluated posterior background activity, focal slowing and IRDA characteristics (frequency, distribution, duration, symmetry and abundance). The clinical diagnosis, state of consciousness and CT brain findings were retrieved from the patients' hospital records. There were 58 patients (33 females; mean age, 58+/-21 years). Twelve (21%) had only focal brain lesions, while 46 (79%) had diffuse brain abnormalities, (15 diffuse structural, 19 metabolic abnormalities, 12 postictal). Normal consciousness and focal EEG slowing were more frequent in patients with focal abnormalities, however, this was not statistically significant. Of the patients with focal abnormality, 11 (92%) had normal posterior background activity either bilaterally (n=4) or contralateral to the focal lesion (n=7). Bilaterally normal posterior background activity was observed in about 30% in both groups. Bilaterally abnormal posterior background activity was apparent in one patient (8%) with focal brain lesion and in 31 patients (67%) with diffuse brain abnormalities (P<0.0001). There were no significant differences in IRDA electrographic features between the focal group and the group with diffuse brain disturbances. We conclude that IRDA morphology cannot distinguish between focal and diffuse brain abnormalities.

The diagnostic aid of routine EEG findings in patients presenting with a presumed first-ever unprovoked seizure.

Data are available on the yield of a single EEG recording in patients with epilepsy but there is little information on EEG findings as an aid in supporting the diagnosis of an epileptic event in patients presenting with a first-ever event suspected of being an unprovoked seizure. We retrieved files of patients above the age of 15 years admitted through the emergency room during 1991-1995 with presumed first-ever unprovoked seizure. There were 91 patients (age 50+/-24; 52 males), of whom 66% had a presumed seizure of unknown origin and 34% had presumed remote symptomatic seizures. About 80% had generalized seizures (primarily or secondarily). In all the patients an EEG had been performed within 48 h of the event. Abnormal EEGs were obtained in 69%, with epileptiform activity in 21% (10% focal, 9% generalized and 2% focal and generalized), slowing in 58% (21% focal, 31% generalized and 7% focal and generalized), and both epileptiform activity and slowing in 10%. Epileptiform activity was most common in younger patients with seizures of unknown origin, compared with older individuals with symptomatic seizures (34, 38 vs. 27%, 7%, P=0.001). We conclude that following a single unprovoked presumed seizure, adults commonly exhibit abnormalities in an EEG recorded close in time to the event. The EEG is particularly helpful in supporting the epileptic nature of the event in younger patients and in those with seizures of unknown origin.

Life-long history of injuries related to seizures.

There is meager information in the literature regarding the characteristics and risk factors for injuries caused during epileptic seizures in adults. Previous studies focused mainly on specific types of injuries incurred, and only few explored associated risk factors. A questionnaire regarding lifetime seizures and their traumatic consequences was administered to 298 consecutive epileptic patients and their caretakers or relatives. Ninety-one of them (30%) have reported trauma: 185 events (age 39.8+/-18 years, 54 males), of which 61 were severe. This translates to one seizure-related injury every 21 patient-years, and a serious injury once every 64 patient-years. The most common site of injury was the head (55% of the events). Blunt injuries occurred most frequently (40%), followed by cuts (28%). Severe injuries included fractures and dislocations (17%), burns (6%), brain concussion (6%), subdural hematoma (3%) and intracerebral hematoma (1%). Most injuries occurred at home. The 91 patients with traumatic events were compared with the 207 epileptic patients without previous trauma (age 37.8+/-14.7 years, 112 males). Patients with seizure-related trauma had significantly earlier onset age of epilepsy. They more commonly had generalized from onset tonic-clonic, complex partial, myoclonic or absence seizures but fewer had partial seizures with secondary generalization. The risk of trauma was mostly related to seizure type (generalized tonic clonic from onset and myoclonic seizures). This information may be helpful for better management of epileptic patients.

Outcome of seizures in the first year of life.

AIM: To determine the frequency and natural history of seizures having an onset during the first year of life. METHODS: A retrospective analysis of the files of all patients treated in the paediatric neurology clinic of our medical centre during 1975-1995. RESULTS: Of our 482 patients with seizure onset prior to age 16 years, the first seizure occurred at age 1-12 months in 80 (16.6%). Of those, 38 (48%) had West syndrome and the rest were classified as follows--partial seizures with or without secondary generalization: 19%, generalized tonic seizures: 8.5%, generalized tonic-clonic seizures: 7.5%, myoclonic: 7.5%, unclassified: 7.5%, and mixed-type seizures: 2%. Follow-up was possible in 91% of the patients. Mean follow-up period from seizure onset was 10 years. Of the non-West syndrome patients who were followed, 19 (50%) were still experiencing seizures at follow-up. Eleven of the 15 patients (73%) with partial seizures and four of the 13 patients (31%) with generalized tonic or tonic-clonic seizures had symptomatic seizures. Of the 14 followed patients with partial seizures, 10 (71%) still had seizures at follow-up, as did three (25%) of the 12 followed patients with generalized tonic or tonic-clonic seizures (p = 0.023). CONCLUSIONS: The partial seizures were most often symptomatic with unfavourable prognosis, while the generalized seizures were either symptomatic and severe or cryptogenic and rapidly responsive to anti-epileptic drugs with good outcome.