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.

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.

Long-term video-EEG in patients with frontal seizures.

The interictal epileptiform discharge (IED) yield of long-term video-EEG (LTVEEG) monitoring is increased compared to a single out-patient EEG, but was not studied specifically in frontal lobe epilepsy. Since IED recording can influence the length of monitoring when seizures are not recorded during LTVEEG, we aimed to assess the IED yield of LTVEEG recording in patients with frontal seizures. We retrospectively reviewed the medical records of 20 patients with frontal seizures during non-invasive LTVEEG in Tel Aviv Medical Center between 2003 and 2008 and compared them with the results of out-patient EEG. The study group included 11 (55%) men and 9 women aged 15-82 years (mean: 27 years). LTVEEG duration ranged between 4 and 29 days (mean: 14 days). IEDs were detected by each of the tests in eight (40%) patients. We conclude that non-invasive LTVEEG and out-patient EEG have a similar diagnostic yield for IEDs in patients with frontal seizures. Therefore, seizures remain the most relevant clinical outcome of LTVEEG.

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.

Video-EEG monitoring of paroxysmal events in the elderly.

OBJECTIVES: To determine the importance of video-EEG monitoring (VEM) in elderly patients with various paroxysmal events. MATERIAL AND METHODS: We retrospectively identified 16 subjects > or = 60 years old out of 834 (1.9%; 7 females, mean age 67.8 +/- 7.7 years), who were admitted to the Video-EEG Unit between 1997 and 2005 and compared data between those with and without epileptic events. RESULTS: Epilepsy was confirmed in six patients, psychogenic non-epileptic seizures (NES) were diagnosed in seven, one patient had NES and epilepsy whereas the recorded events were non-conclusive in two. NES patients had a higher predisposition to psychiatric disturbances (P<0.02). Following VEM and management alteration, the frequency of monthly events decreased significantly for the cohort as a whole (P<0.001). VEM directly influenced the diagnosis, treatment and outcome of 14 of 16 (88%) patients. CONCLUSION: Video-EEM plays a vital role in the evaluation of paroxysmal events in the elderly, but is vastly underutilized in this population group.

Is there any correlation between severity of epilepsy and cognitive abilities in patients with temporal lobe epilepsy?

Frequent refractory seizures may cause cognitive deterioration when they present at an early age, especially in infants. The findings of previous studies designed to examine the impact of repetitive seizures on cognition in adolescents and adults, however, have shown wide variation. We analyzed the data of neuropsychological evaluations of patients before they underwent temporal lobe resection because of refractory seizure disorder in our institution from 1998 to 2001. Forty-four consecutive patients aged 12-48 years underwent a comprehensive neuropsychological evaluation that included a battery of selected visual and verbal memory tests. Statistical analysis revealed no significant correlation between disease-related parameters, such as age of onset, duration of active disease, estimated cumulative number of complex partial seizures and secondarily generalized seizures, and the results of neuropsychological tests. These findings support the hypothesis that factors other than repetitive seizures are responsible for cognitive dysfunction among adolescents and adults.

Cortical lesions associated with transient neurological symptoms - not always a matter of cause and effect.

The occurrence of transient recurrent stereotypical neurological events mandates the exclusion of an underlying brain lesion. When imaging studies demonstrate the presence of a structural brain lesion, a cause and effect relationship between the two entities is assumed, and the decision for surgical intervention may then follow almost automatically. We describe five patients with transient neurological events suspected as being seizures that were referred for surgery because of an associated structural brain lesion. Video electroencephalographic recordings revealed that the events that brought these patients to neurosurgical attention were non-epileptic seizures. None of these patients underwent surgical intervention, and all were referred for behavioral therapy. Therefore, even in the presence of a confirmed brain lesion, the presenting paroxysmal events may be of a non-organic origin and should not necessarily be assumed to be caused by the concomitantly existing structural abnormality.

Auditory hallucinations in Parkinson's disease.

Whereas visual hallucinations are often found among patients with Parkinson's disease, the occurrence of auditory hallucinations has never been systematically documented. The occurrence, past and present, of auditory hallucinations has been studied in 121 consecutive patients with Parkinson's disease attending a movement disorders clinic. The cognitive state was evaluated using the short mental test (SMT). Hallucinations were reported for 45 patients (37%); 35 (29%) had only visual hallucinations and 10 (8%) both visual and auditory hallucinations. No patient reported auditory hallucinations unaccompanied by visual hallucinations. The auditory hallucinations occurred repeatedly, consisting of human voices. They were non-imperative (n=9), non-paranoid (n=9), and often incomprehensible (n=5). They were not obviously influenced by the patients' age, duration of disease, or treatment with levodopa. Cognitive impairment was more common among hallucinating patients (64%, 50%, and 25% among patients with visual hallucinations, auditory hallucinations, and nonhallucinating parkinsonian patients respectively). Depression necessitating antidepressants was present in five of 10 and other psychotic features in six patients with auditory hallucinations. It is concluded that auditory hallucinations occur in Parkinson's disease, particularly in patients who also have visual hallucinations and are cognitively impaired.

Apolipoprotein E4 in Parkinson disease and dementia: new data and meta-analysis of published studies.

The authors examined whether the epsilon4 allele might be associated with dementia in Parkinson disease (PD), given that the dementia of PD shares neuroanatomic and neurochemical features with Alzheimer disease (AD) and that many recent studies have found a high prevalence of the epsilon4 allele of apolipoprotein E (ApoE) in AD. The authors examined patients with PD (n=125, 47 demented) and unrelated controls (n=93) using a short mental test. DNA was obtained from blood leukocytes. The relevant portion of the apolipoprotein E (ApoE) gene was amplified by polymerase chain reaction, and the epsilon4 allele was identified using a restriction enzyme. The frequency of the ApoE epsilon4 allele in demented patients with PD (14%) was not greater than that in nondemented patients (17%), whereas patients with PD as a whole showed a trend toward a higher epsilon4 allele frequency (16%) than age-matched controls (10%, p=0.07). The epsilon4 allele frequency in nondemented patients with PD was significantly higher than in controls (p=0.055). These results and the meta-analysis of four published reports fail to support the hypothesis that the epsilon4 allele is associated with dementia in PD.