Early versus late antiepileptic drug withdrawal following temporal lobectomy.

PURPOSE: To compare the seizure outcome following early and late complete antiepileptic drug (AED) withdrawal following anterior temporal lobectomy (ATL) for mesial temporal lobe epilepsy (MTLE). METHOD: All the patients who were seizure free for one year following ATL were offered early or late AED withdrawal. AEDs were discontinued starting at one year in those who opted for early withdrawal. Patients who opted for late withdrawal were continued on single AED for three years following surgery before attempting complete discontinuation. RESULTS: Of the 135 study patients, 65 opted for early AED withdrawal and 70 for late withdrawal. The mean postoperative follow-up duration was 10.4 ± 1.3 (Range, 8-12) years. At three years following surgery, seizure recurrence occurred in 23 (35.4 %) patients in the early withdrawal group and in 10 (14.3 %) patients in late withdrawal group (p = 0.005; relative risk [RR], 2.48; 95 % confidence interval [CI], 1.28-4.80). At last follow-up, 27 (41.5 %) patients in the early withdrawal group and 26 (37.1 %) in late withdrawal group had recurrence (p = 0.60; RR, 1.12, 95 % CI, 0.74-1.70). At last followup, 80 (59.3 %) patients were off AEDs. During the terminal one year, 123 (91 %) patients were seizure free, similar in the two groups. CONCLUSIONS: This nonrandomized controlled study suggests that early complete AED withdrawal starting one year following ATL is associated with a higher risk of early seizure recurrence. However, long term seizure outcome is similar in early and late AED withdrawal groups.

Predictors of seizure outcome following resective surgery for drug-resistant epilepsy associated with focal gliosis.

OBJECTIVEThe authors studied the clinical characteristics and postoperative outcomes of drug-resistant epilepsy associated with focal gliosis.METHODSFrom their epilepsy surgery database, the authors selected the patients with drug-resistant epilepsy and MRI-defined focal gliosis who underwent focal resective surgery. All patients underwent standard presurgical evaluation. Intracranial electroencephalography (EEG) was performed in patients with discordant presurgical data, ill-defined lesions, and lesions close to eloquent regions. Completeness of resection was defined on the basis of extraoperative and intraoperative electrocorticography studies. Favorable postoperative outcome was defined as Engel class I outcome during the last 2 years of follow-up.RESULTSSixty-six patients fulfilled inclusion criteria. An initial precipitating injury was present in 38 (57.6%) patients, mainly in the form of perinatal injury (n = 10), trauma (n = 10), and meningoencephalitis (n = 8). Gliosis involved a single lobe in 38 (57.6%) patients and 2 adjacent lobes in 14 (21.2%) patients; the remaining 14 (21.2%) patients had multilobar gliosis. In patients with unilobar or bilobar gliosis, the posterior region of the head was involved in 34 (65%) patients and the frontal lobes in 12 (23%) patients. During a median follow-up of 4 years (range 2-9 years), 41 (62.1%) patients had favorable outcome. On multivariate analysis, the presence of a well-defined aura (p = 0.019), electrocorticographically defined completeness of resection (p = 0.024), and normal postoperative EEG findings at 1 year (p = 0.003) were predictive of favorable postoperative seizure outcome.CONCLUSIONSFocal gliosis is a common etiology for drug-resistant extratemporal epilepsy in developing countries and is most often located in the posterior region of the head. The majority of these patients have perinatal injuries or neurological infections as initial precipitating injuries. Patients with focal gliosis have good postoperative seizure outcomes after well-planned resective surgery.

Optimal timing and differential significance of postoperative awake and sleep EEG to predict seizure outcome after temporal lobectomy.

OBJECTIVE: To evaluate the prognostic value of postoperative EEGs to estimate post anterior temporal lobectomy (ATL) seizure outcome. METHODS: We studied postoperative EEGs in 325 consecutive patients who had minimum five years of post-ATL followup. Interictal epileptiform discharges (IEDs) present only during sleep were classified as sleep IEDs. We defined favorable final-year outcome as no seizures during the final one year and favorable absolute-postoperative outcome as no seizures during the entire postoperative period. RESULTS: At mean follow-up of 7.3 ±â€¯1.8 years, 281 (86.5%) patients had favorable final-year outcome while 161 (49.5%) had favorable absolute-postoperative outcome. IEDs on three months and one year EEG were associated with unfavorable outcomes while IEDs at 7th day had no association with outcomes. Sleep record increased the yield of IEDs by 30% at each time-point without compromising predictive value. EEG at one year predicted the risk of seizure recurrence on drug withdrawal. CONCLUSION: While EEG at three months and at one-year after ATL predicted seizure outcome, EEG at 7th day was not helpful. Sleep record increases the sensitivity of postoperative EEG without compromising specificity. SIGNIFICANCE: Both awake and sleep EEG provide useful information in postoperative period following ATL.

Outcome after seizure recurrence on antiepileptic drug withdrawal following temporal lobectomy.

OBJECTIVE: To study the long-term outcome following seizure recurrence on antiepileptic drug (AED) withdrawal after anterior temporal lobectomy for mesial temporal lobe epilepsy. METHODS: We retrospectively studied the AED profile of patients who had a minimum of 5 years of postoperative follow-up after anterior temporal lobectomy for mesial temporal lobe epilepsy. Only those patients with hippocampal sclerosis or normal MRI were included. AED withdrawal was initiated at 3 months in patients on ≥2 drugs and at 1 year for patients on a single drug. RESULTS: Three hundred eighty-four patients with median postoperative follow-up of 12 years (range, 7-17 years) were included. Of them, 316 patients (82.3%) were seizure-free during the terminal 1 year. AED withdrawal was attempted in 326 patients (84.9%). At last follow-up, AEDs were discontinued in 207 patients (53.9%). Seizure recurrence occurred in 92 patients (28.2%) on attempted withdrawal. After a median postrecurrence follow-up of 7 years, 79 (86%) of them were seizure-free during the terminal 2 years. AEDs could be stopped in 17 patients (18.5%) and doses were reduced in another 57 patients (62%). Patients with febrile seizures, normal postoperative EEG at 1 year, and duration of epilepsy of <20 years (FND20 score) had 17% risk of seizure recurrence on attempted AED withdrawal. We also formulated a score to predict the chances of AED freedom for the whole cohort. CONCLUSION: Patients with seizure recurrence on AED withdrawal have good outcome with 86% becoming seizure-free and 18% becoming drug-free after initial recurrence. A FND20 score helps in predicting recurrence on AED withdrawal.

Efficacy and Safety of Intravenous Tenecteplase Bolus in Acute Ischemic Stroke: Results of Two Open-Label, Multicenter Trials.

BACKGROUND: Tenecteplase (TNK-tPA) is a promising third-generation plasminogen activator, because of its greater fibrin specificity and longer half-life than alteplase. There is a paucity of studies on intravenous thrombolysis using TNK-tPA in developing countries. The present study has been undertaken to compare the efficacy and safety of TNK-tPA with alteplase. METHODS: Two studies were conducted. Study I was an open-label, randomized study in which two doses of TNK-tPA (0.1 and 0.2 mg/kg) were compared. Study II was an open-label study in which TNK-tPA 0.2 mg/kg bolus was compared with historical controls. The primary endpoint for study I and study II was an improvement of ≥ 8 points or a score of 0 on the National Institutes of Health Stroke Scale (NIHSS) [major neurological improvement (MNI)] at 24 h. Secondary endpoints for both studies were neurological improvement as assessed using the NIHSS score, modified Rankin Scale (mRS) score and the Barthel Index (BI) on days 7, 30 and 90. Minimal disability was defined as an mRS score of 0 or 1 and good functional recovery as a BI score of 50-90. Safety was assessed by the proportion of patients having symptomatic intracranial hemorrhage (sICH) within 36 h and asymptomatic intracranial hemorrhage at 48 h after treatment. RESULTS: In study I, 20 patients received 0.1 mg/kg and 30 received 0.2 mg/kg TNK-tPA. There was no significant difference in MNI at 24 h between 0.1 and 0.2 mg/kg TNK-tPA doses. The patients given 0.2 mg/kg TNK-tPA had a significantly better 3-month outcome (minimal disability, p = 0.007). There was no sICH in study I. In study II, 62 patients (one lost to follow-up) received 0.2 mg/kg TNK-tPA. MNI was noted in ten patients (16.4%), 3-month minimal disability was noted in 37 patients (60.7%), and good functional recovery was seen in 33 patients (54.1%). sICH occurred in one patient, and four patients died. Pooled data of patients in study I and study II receiving 0.2 mg/kg TNK-tPA were compared with data from the historical National Institute of Neurological Disorders and Stroke (NINDS) trial. For comparison, the primary endpoint of the NINDS trial (improvement on NIHSS of ≥ 4 points or a score of 0 at 24 h) was taken. The primary endpoint though was not significantly different (58.2% vs. 47%, p = 0.08), but with TNK-tPA, greater neurological improvement, minimal disability (70.3 vs. 39%, p < 0.001) and good functional recovery (36.3 vs. 16%, p < 0.001) was noted at 3 months. There was a lower incidence of sICH (1.1 vs. 6.4%, p = 0.05) and lower 3-month mortality (5.5 vs. 17%, p = 0.01) noted with TNK-tPA compared with alteplase. CONCLUSIONS: Intravenous TNK-tPA 0.2 mg/kg administered within 3 hours of symptom onset seems to be well tolerated and effective option in patients with acute ischemic stroke. TRIAL REGISTRATION: Clinical Trials Registry-India, www.ctri.nic.in ; unique identifiers: CTRI/2009/091/000251 and CTRI/2015/02/005556.

Interictal regional paroxysmal fast activity on scalp EEG is common in patients with underlying gliosis.

OBJECTIVE: Interictal regional paroxysmal fast activity (RPFA) on scalp EEG is common in patients with focal cortical dysplasia (FCD). Little data exists regarding the presence of RPFA in other etiologies. METHODS: We studied the association between RPFA and etiology on MRI in patients with drug resistant focal epilepsy undergoing presurgical evaluation in 2011. RPFA was defined as ≥3 consecutive spikes with a frequency of ≥10 Hz lasting ≥300 ms but <4 s. RESULTS: 626 patients fulfilled the inclusion criteria. Of these, 138 (22%) patients had RPFA while rest had other interictal epileptiform discharges (IEDs). RPFA was located at posterior head region in 52.2% patients, frontal regions in 24.6% patients and over temporal regions in 17.4% patients. Focal gliosis (61, 44%) and FCD (27, 19%) were common etiologies in patients with RPFA. Compared to patients with other IEDs, patients with RPFA were more likely to have focal gliosis (61/138 vs. 39/488; p < 0.0001) or FCD (27/138 vs 37/488; p < 0.001) as the etiology of epilepsy. CONCLUSION: In developing countries, focal gliosis is more common than FCD as the underlying etiology in patients with RPFA on scalp EEG. SIGNIFICANCE: Focal gliosis should be considered as one of the common substrate for RPFA on scalp EEG.

Reversible Holmes' tremor due to spontaneous intracranial hypotension.

Holmes' tremor is a low-frequency hand tremor and has varying amplitude at different phases of motion. It is usually unilateral and does not respond satisfactorily to drugs and thus considered irreversible. Structural lesions in the thalamus and brainstem or cerebellum are usually responsible for Holmes' tremor. We present a 23-year-old woman who presented with unilateral Holmes' tremor. She also had hypersomnolence and headache in the sitting posture. Her brain imaging showed brain sagging and deep brain swelling due to spontaneous intracranial hypotension (SIH). She was managed conservatively and had a total clinical and radiological recovery. The brain sagging with the consequent distortion of the midbrain and diencephalon was responsible for this clinical presentation. SIH may be considered as one of the reversible causes of Holmes' tremor.

Hypertrophic pachymeningitis in a patient with Takayasu arteritis: One more association?

Hypertrophic pachymeningitis (HP) is a rare chronic inflammatory disease of the dura mater, described in association with various infections, systemic vasculitides such as Wegener's granulomatosis and giant cell arteritis. However, HP in association with Takayasu arteritis (TA) has not been described. We report a young woman who presented with headache, seizures, and right third and fourth cranial neuropathy. Magnetic resonance imaging of the brain showed HP in bifrontal and right temporal region extending to cavernous sinus. She was also found to have systemic hypertension, stenosis of left subclavian, and left renal artery with narrowing of abdominal aorta, satisfying the diagnostic criteria for TA. A detailed evaluation for secondary causes of HP failed to reveal an alternative etiology. This report describes an unusual association of HP in a patient with TA, also emphasizing that seizures and cranial neuropathy may further expand the spectrum of neurological manifestations in patients with TA.

Kinaesthetic ipsilateral and crossed extensor plantar response: A new way to elicit upgoing toe sign (Babinski response)?

We describe a phenomenon of "kinaesthetic extensor plantar response" in advanced pyramidal dysfunction, an interesting observation noted in a patient with dorsal myelopathy. A 44-year-old woman presented with one-year history of gradually progressive weakness and stiffness of both lower limbs along with urge incontinence of urine. Examination showed spontaneous elicitation of extensor plantar response while assessing the tone by rolling method as well as on noxious stimulation of the thigh. Magnetic resonance imaging (MRI) of the dorsal spine and digital subtraction angiography showed the presence of spinal dural arteriovenous fistula causing myelopathy. This case exemplifies the fact that in advanced pyramidal dysfunction, not only the receptive field of Babinski reflex may extend to the leg or thigh, but may also integrate with other modalities of stimulation, such as the rolling movement. The possible underlying pathophysiology of such a phenomenon is discussed.

Evolution and long term outcome in patients presenting with large demyelinating lesions as their first clinical event.

OBJECTIVES: To describe the long term evolution and outcome of a homogeneous cohort of patients (n=14) with large demyelinating lesions (LDLs) as the first clinical event from a group of idiopathic inflammatory demyelinating diseases of central nervous system. METHODS: Detailed review of LDLs from December 2002-January 2007 was made. Patients had at least two magnetic resonance imaging (MRI) and minimum follow-up of 2years. The disability was assessed using Estimated Expanded Disability Status Scale (EDSS) and Rappaport Disability Rating Scale (DRS) at onset and last follow-up. RESULTS: Fourteen consecutive LDL patients (male=7), with mean age 32.7years and mean follow-up of 45.5months were included. Motor deficits (79%) and cognitive symptoms (43%) marked the onset, none had optic neuritis. All except two responded to steroids. Follow-up MRI showed complete resolution in 43%, 57% showing marked reduction in size. On follow-up, 2 relapsed. Mean EDSS and DRS at presentation were 5.93 and 9.07 and at last follow-up were 1.75 and 2.25 (p<0.001). CONCLUSIONS: Our data suggests that, patients presenting with LDLs as their first clinical event behaves distinctly in their presentation, imaging characteristics, prognosis and long term outcome as compared to MS and ADEM. Albeit significant disability at the onset, these patients show an excellent response to treatment with good functional recovery in long term and rare relapses.

An overview of biomarkers in Alzheimer's disease.

Alzheimer's disease (AD) is the commonest progressive, dementing neurodegenerative disease in elderly, which affects innumerable people each year, and these numbers are likely to further increase as the population ages. In addition to the financial burden of AD on health care system, the disease has powerful emotional impact on caregivers and families of those afflicted. In this advancing era of AD research, with the availability of new treatment strategies having disease-modifying effects, there is growing need for the early diagnosis in AD, often hampered by paucity of biomarkers of AD. Various candidate biomarkers for AD have been developed that can detect patients with AD at an early stage. In the recent years, the search for an ideal biomarker has undergone a rapid evolution. Novel technologies in proteomics, genomics, and imaging techniques further expand the role of a biomarker not only in early diagnosis, but also in monitoring the response to various treatments. However, the availability of sensitive and specific biomarkers requires the method to be standardized so as to be able to compare the results across studies. Inspite of tremendous advances in this field the quest for an "ideal biomarker" still continues. In this review, we will discuss the various candidate markers in five spheres namely biochemical, neuroanatomical, metabolic, genetic and neuropsychological, and their current status and limitations in AD diagnosis.