KBG syndrome mimicking genetic generalized epilepsy.

•Several conditions may mimic Genetic Generalized Epilepsy GGE.•GGE is less frequently misdiagnosed compared to other subtypes of epilepsy.•KBG syndrome is a rare autosomal dominant condition.•KBG syndrome may mimic GGE.

Diagnostic Yield of Routine EEG in Adults with Active Epilepsy

Routine electroencephalogram (rEEG) is an important investigation in suspected seizures but can be normal in people with epilepsy. The diagnostic yield of rEEG varies considerably according to the patient group studied. We aimed to estimate the diagnostic yield of rEEG in a real-world cohort of adults with active epilepsy­a population not previously reported. This single centre study evaluated neurophysiology findings for adults with prolonged inpatient video EEG (vEEG)-confirmed active epilepsy, who had at least one prior rEEG. Sixty-eight patients had a total of 171 rEEGs, of which 93 (54.4%) were normal, 42 (24.6%) found non-specific abnormalities and 36 (21.1%) captured interictal epileptiform abnormalities (IIEAs). Serial rEEGs revealed a 22.1% yield of IIEAs on the first test, with the cumulative yield peaking at 33.8% on the fourth rEEG. This study adds to existing evidence regarding the limited diagnostic usefulness of serial rEEG in patients with active epilepsy.

Investment in epilepsy monitoring units improves epilepsy care-experience in a regional neuroscience centre.

An evaluation of the clinical yield of inpatient long-term video-EEG (vEEG) in a new epilepsy monitoring unit (EMU) was undertaken, with findings compared to the centre's prior method of bedside vEEG recording in a standard neurology ward, as reported in 2004. A retrospective analysis of neurophysiology reports for all adults who underwent elective vEEG monitoring in the EMU at Cork University Hospital between January 2015 and July 2016 was conducted. Of 115 vEEG studies in the EMU, 100 (87.0%) were deemed diagnostically conclusive, 14 (12.2%) failed to catch any clinical events and showed normal EEG throughout, and one (0.9%) captured spells of unclear clinical significance - the corresponding figures reported in 2004 for bedside vEEGs were 21.3%, 77% and 1.6%, respectively. The EMU offers a more effective method of recording inpatient vEEG, which aids decision-making and improves clinical outcomes. Some evidence-based measures which could further enhance diagnostic yield are discussed.

Assessment of the usefulness of magnetic resonance brain imaging in patients presenting with acute seizures.

BACKGROUND: Magnetic Resonance Imaging (MRI) is increasingly available as a tool for assessment of patients presenting to acute services with seizures. AIMS: We set out to prospectively determine the usefulness of early MRI brain in a cohort of patients presenting with acute seizures. METHODS: We examined the MR imaging studies performed in patients admitted solely because of acute seizures to Cork University Hospital over a 12-month period. The main aim of the study was to determine if the MRI established the proximate cause for the patient's recent seizure. We identified 91 patients who underwent MRI brain within 48 h of admission for seizures. RESULTS: Of the 91 studies, 51 were normal (56 %). The remaining 40 studies were abnormal as follows: microvascular disease (usually moderate/severe) (n = 19), post-traumatic gliosis (n = 7), remote symptomatic lesion (n = 6), primary brain tumour (n = 5), venous sinus thrombosis (n = 3), developmental lesion (n = 3), post-surgical gliosis (n = 3) and single cases of demyelination, unilateral hippocampal sclerosis, lobar haemorrhage and metastatic malignant melanoma. Abnormalities in diffusion-weighted sequences that were attributable to prolonged ictal activity were seen in nine patients, all of who had significant ongoing clinical deficits, most commonly delirium. Of the 40 patients with abnormal MRI studies, seven patients had unremarkable CT brain. MR brain imaging revealed the underlying cause for acute seizures in 44 % of patients. CT brain imaging failed to detect the cause of the acute seizures in 19 % of patients in whom subsequent MRI established the cause. CONCLUSION: This study emphasises the importance of obtaining optimal imaging in people admitted with acute seizures.

Periodic epileptiform discharges in hypoxic encephalopathy: BiPLEDs and GPEDs as a poor prognosis for survival.

INTRODUCTION: Electrophysiologic tests in hypoxic encephalopathy consist of EEG and evoked/event-related potential studies. In most studies the generalized periodic epileptiform complexes have been reported combined with other EEG patterns and were indicators of a poor outcome in different etiologies of hypoxic encephalopathy (HE), but these have rarely been examined independently. METHODOLOGY: We analyzed from 2000 to 2007 the outcome of patients with HE and generalized periodic epileptiform complexes. We abstracted and tabulated clinical information, imaging findings, and outcome from the medical records. RESULTS: We found 52 patients in our database. Fourteen patients (eight BiPLEDs and six GPEDs) were associated with HE. Patients with BIPLEDs were 68+/-19.4 years old, 5 female (62%) and 3 (38%) men. GPEDs patients were 52.5+/-19.1 years old, 2 women (20%) and 4 (80%) men. Myocardial infarction and ventricular tachycardia were responsible of 57% of the HE cases. Neuroimaging studies in both groups showed cortical structural lesions in 84%. All patients were comatose and died. Two GPEDs patients developed status epilepticus. CONCLUSION: GPEDs and BIPLEDs after an anoxic insult carried a poor prognosis for survival. Aggressive treatment of patients may not be warranted when these EEG patterns are seen after anoxic brain injury.

Consideration of epilepsy surgery in adults should be independent of age.

OBJECTIVES: Epilepsy surgery is performed less frequently in persons over 45 years of age than in younger individuals, probably reflecting biases among patients, referring physicians and neurologists. METHODS: We report on a clinically heterogeneous cohort of patients aged 45 years or older who underwent epilepsy surgery for medically intractable epilepsy. RESULTS: Over a 15-year period, 42 patients with a mean duration of epilepsy of 27.3 years underwent elective surgery. The mean follow-up period was 48 months. Thirty-two patients had an Engel class I outcome, of which 23 were totally seizure-free (Ia). Six patients had a class II outcome (rare disabling seizures), one had a class III outcome (worthwhile improvement), and three had a class IV outcome (no worthwhile improvement). The majority of patients reported an improved quality of life and satisfaction with the epilepsy surgery. A subjective improvement in cognition was reported in 7 patients while a decline was reported in 10 patients. New neuropsychiatric difficulties were reported in three patients while three patients reported improved anxiety after surgery. Only one patient became newly employed after surgery while 23 returned to driving. Permanent complications occurred in four patients (thalamic infarct during a Wada test (n=1) and asymptomatic visual field defect (n=3)). CONCLUSIONS: We report a favorable outcome from epilepsy surgery in a large series of older adults and conclude that age per se is not a contraindication to epilepsy surgery. We emphasize the lack of correlation between outcome from surgery and pre-operative duration of epilepsy.

Stereotactic cortical resection in non-lesional extra-temporal partial epilepsy.

The presentation and treatment of a patient with extra-temporal non-lesional partial epilepsy is discussed herein. His clinical semiology was consistent with supplementary motor area seizures; however, MR imaging did not demonstrate a lesion. A region of stable cortical glucose hypermetabolism in the left frontal region was noted with 2-fluoro-2-deoxy-D-glucose (FDG)-PET. This was consistent with the frequent interictal discharges evident over the left fronto-temporal region and the stereotypic high amplitude ictal discharges arising with highest amplitude from the left frontal region. Epileptiform activity evident on an intracranial 64-point subdural recording grid placed over the left dorsolateral frontal cortex confirmed a distribution concordant with FDG-PET findings. The subsequent resection was guided by the PET and EEG findings rather than structural MR imaging, and a limited cortical resection led to an immediate and substantial reduction in seizure frequency.

Audit of an inpatient neurology consultation service in a tertiary referral centre: value of the consulting neurologist.

The Mater Misericordiae Hospital is a 575-bed tertiary referral centre with busy medical and surgical subspecialty services (including the national cardiac, cardiothoracic, spinal cord injury and pulmonary hypertension units). An audit of in-patient referrals to a neurology service was carried out over the twelve-month period of January to December 2002 inclusively. Five hundred and seventy seven inpatients were evaluated and managed in conjunction with the referring services. Consultation by the neurological service led to a significant contribution in the management of clinical cases in one of three ways: establishing a de novo diagnosis in patients admitted with active neurological symptoms where no working diagnosis exists (40.7% of referrals), significant alteration in diagnosis where the referring service have already established a specific working diagnosis (11.1% of referrals), or offering advice in the ongoing management of active neurological symptoms when the diagnosis is historically established and secure (48.2% of referrals). In order of frequency the most common reason for referral was stroke (131 cases (22.7%)), seizures unrelated to alcohol (59 cases (10.2%)), alcohol-related neurological problems (55 cases (9.5%)), movement disorders (41 cases (7.1%)), neuromuscular (40 cases (6.9%)), coma (35 cases (6%)), disorders of cognition (31 cases (5.3%)), acute headache (28 case (4.8%)) and functional neurological syndromes (26 cases (4.5%)). This audit highlights the value of a consulting neurology service in a multidisciplinary tertiary referral setting.

Fatal presentation of ornithine transcarbamylase deficiency in a 62-year-old man and family studies.

Ornithine transcarbamylase deficiency (OTCD) resulting from deficiency of the mitochondrial enzyme OTC shows extensive phenotypic heterogeneity influenced by allelic heterogeneity and modifying environmental influences such as protein intake. We report the fatal late-onset presentation of OTCD in a 62-year-old man with the V337L mutation, a previous presentation in his grandson and negative clinical and biochemical screening of the proband's three daughters.

Concurrent hereditary haemochromatosis and idiopathic Parkinson's disease: a case report series.

Hereditary haemochromatosis (HH) is a genetic disorder in which abnormal iron handling leads to excessive iron accumulation in systemic tissues. Magnetic resonance imaging studies suggest excess iron deposition in the basal ganglia of patients with HH. The symptoms of neurological complications of HH include cognitive decline, gait difficulties, cerebellar ataxia, and extrapyramidal dysfunction, but idiopathic Parkinson's disease, in which brain iron deposition is normal, has not been reported. We describe four patients with concurrent HH and IPD. Although three of the cases had risk factors for cerebrovascular and cardiovascular disease, computed tomography did not show ischaemic changes in the basal ganglia. We speculate that in these cases, abnormal deposition of iron in the basal ganglia induced the symptoms of IPD.

Effect of blood pH and ischemia on kinetic constants for cerebral glucose transport.

In 117 experiments, the isolated canine brain was subjected either to 4-min pulses with blood ranging from pH 6.8 to 7.8, 30 min of hypoxia (PaO2 30 mmHg or 40 mmHg), or 30 min of complete ischemia followed by 60 min of perfusion with normal oxygenated blood. Unidirectional and net glucose fluxes were measured under all experimental conditions, and kinetic constants were calculated for unidirectional transport at each pH and after ischemia. In brains perfused with blood having a PaO2 of 30 or 40 mmHg, we observed a 58 and a 55% increase, respectively, in the net flux; however, there was no significant change in the unidirectional flux either during hypoxia or during the recovery period. Exposure of the brains to blood with a pH of 6.8, 7.0, and 7.2 had no effect on the unidirectional flux; however, as pH was raised above 7.4 both the Km and Vmax increased, reaching a maximum of 12.06 +/- 2.34 mM and 2.38 +/- 0.28 mumol X g-1 X min-1, respectively, at pH 7.8. The V/K ratio was unchanged. After 30 min of ischemia, there was a significant change (P less than 0.05) in the Km of the unidirectional glucose transport process from a control value of 5.84 +/- 1.75 mM to 17.40 +/- 5.50. These studies suggest that unidirectional flux is impaired after ischemia due to a decrease in the carrier's affinity for glucose; however, the observed changes are apparently unrelated to a fall in tissue pH. A similar mechanism is believed to be responsible for the decrease in unidirectional glucose flux after hypoxia.

Increased blood oxygen affinity decreases canine brain oxygen consumption.

We have studied the effect of increased blood O2 affinity on O2 delivery to the isolated canine brain. After surgical isolation, the brain, enclosed in the calvarium, was perfused alternately from two pump-oxygenators with normal blood (P 50 [7.4] = 30 +/- 2 torr [S.D.]) and with blood whose P50 was reduced to 18 +/- 2 torr by carbamylation. [Hb], acid-base balance, blood gases, and flow rate were carefully matched in the two circuits. Although blood [Hb] was reduced to approximately 10 gm/dl, other perfusion variables such as CBF (65 +/- 6 ml/min/100 gm) and arterial blood oxygen saturation (96% to 99%) were normal for the dog. Under these conditions cerebral VO2 (Fick) averaged 3.87 +/- 0.73 ml/min/100 mg (S.D.) with control blood and 2.94 +/- 0.69 with low P50 blood (mean delta = 24%, n = 14, p less than 0.001), and PVO2 averaged 31 +/- 2 and 21 +/- 2 torr, respectively (p less than 0.001). The fall in VO2 during low P50 perfusion was associated with a decrease in [A-V]O2 difference and a rise in CVO2 of 1.2 ml/dl, which suggests that O2 extraction at PVO2 approximately 20 torr is curtailed. The EEG, previously shown to correlate with VO2 in this model, invariably deteriorated after 30 to 60 sec of low P50 perfusion and improved in 30 to 60 sec after reperfusion with normal blood. CBV increased by 0.9 ml/100 gm during low P50 perfusion, implying capillary recruitment. In a parallel series of experiments, four brains were alternately perfused with normal blood (pH 7.41, PCO2 38 torr, P50 [7.4] = 30 torr) and alkalotic blood (pH 7.98, PCO2 39 torr, P50 [7.98] = 17.3 torr). With flow rates equal for both normal and experimental blood, PVO2 averaged 31 +/- 4 (S.D.) and 21 +/- 3 torr (p less than 0.001), respectively, and VO2 averaged 4.33 +/- 0.52 ml/min/100 gm and 3.18 +/- 0.52 (p less than 0.001). With pH at 7.4 and 7.8, VO2 averaged 4.42 +/- 0.77 ml/min/100 gm and 3.66 +/- 0.99, respectively (p less than 0.01). The data indicate that a reduced P50 limits O2 diffusion to brain at a normal but fixed blood flow rate despite capillary recruitment.

Brain metabolism after 30 minutes of hypoxic or anoxic perfusion or ischemia.

In 48 separate experiments, isolated canine brain preparations were subjected to 30 min of either hypoxic (PaO2 congruent to 20 mmHg) perfusion, anoxic (PaO2 < 10 mmHg) perfusion, or total ischemia followed by reperfusion for up to 2 h with normal oxygenated blood. Unlike ischemia and anoxia, energy metabolism was sufficient during hypoxia to maintain substantial levels of ATP (48% of normal), sustain normal ion gradients, and prevent edema formation. Posthypoxia metabolism was adequate to clear accumulated lactate, enable recovery of normal tissue glucose levels, and allow return to normal levels of glycolytic intermediates. Although not as complete as that following hypoxia, recovery from cerebral edema and restoration of metabolism were better in ischemic than anoxic cortex. The reduced oxygen uptake in all groups during reoxygenation (55% of normal) indicates that all have a diminished capacity for energy metabolism. The ATP levels recovered more rapidly after 15 min of reoxygenation in the anoxic (57% of normal) than in the ischemic (21% of normal) group. Thus ATP does not appear to be directly related to recovery from edema.

Naloxone antagonizes narcotic self blockade of emesis in the cat.

Morphine, levorphanol, fentanyl and methadone given by intracerebroventricular (i.c.v.) injection blocked the vomiting response to a standard emetic test dose of apomorphine subsequently injected i.c.v. Of these narcotics, only morphine initially evoked vomiting. Systemic pretreatment with naloxone (5 mg/kg i.p. or i.v.) uniformly abolished the antiemetic activity of all the represented narcotic agents, moreover, naloxone thus administered was followed consistently by emetic responses to those narcotics which separately failed to evoke vomiting. When naloxone was injected i.c.v. in addition to being given systemically, both antiemetic and emetic activities of the narcotic agents were essentially abolished, whereas apomorphine continued to evoke vomiting. In the presence of systemic naloxone, given to counteract self-blockade of vomiting, the narcotics were shown to induce vomiting through excitation of the medullary emetic chemoreceptor trigger zone and emetic receptor tolerance as well as cross-tolerance developed acutely. The present differentiation by naloxone of the emetic and antiemetic properties of narcotic agents placed in the cerebrospinal fluid indicates that the opposing narcotic actions are exercised at different sites in the brain and that the narcotic receptor specificity of the chemoreceptor trigger zone does not encompass the emetic action of apomorphine.