Literature Monitor

Epilepsy Surgery Reduces Seizures At 10 Years
One decade after undergoing epilepsy surgery, about half of patients remain free of all seizures except simple partial seizures (SPS), researchers reported iLiterature Monitorn the October 15 issue of Lancet.

Jane de Tisi, of the National Hospital for Neurology and Neurosurgery, London, and colleagues followed 615 adult patients for a median of eight years after epilepsy surgery. Of these patients, 497 had anterior temporal resection, 40 had temporal lesionectomy, 40 had extratemporal lesionectomy, 20 had extratemporal resection, 11 had hemispherectomy, and seven had a palliative procedure.

Freedom from non-SPS seizures occurred in 52% of patients at five years and 47% of patients at 10 years. Eighty-two percent of patients had at least one year of freedom from non-SPS seizures, and 73% of patients had at least one year of freedom from all seizures, including SPS.

Patients who experienced SPS within two years following surgery were twice as likely as other patients to experience subsequent seizures with impaired awareness. Relapse was less likely among patients with longer periods of seizure freedom, and remission was less likely among patients with longer periods of experiencing seizures. Seizure recurrence was twice as likely in patients with extratemporal resections as in patients with anterior temporal resections.

Late seizure remission was associated with the use of a previously unused antiepileptic drug in 18 (19%) of 93 patients who experienced such a remission following initial seizures or transient relapse. Of the 365 patients who were seizure-free at their latest follow-up, 104 (28%) had discontinued use of antiepileptic drugs.

“For seizure outcome, surgery is successful for many individuals in whom antiepileptic drugs have not been effective, but further improvements need to be made to presurgical assessment to further increase rates of success,” the investigators concluded. The predictive value of SPS following surgery “has implications for decisions to discontinue antiepileptic drugs in patients with only SPS,” added Ahmed-Ramadan Sadek, MD, and William Peter Gray, MD, both from the University of Southampton, UK, in an accompanying comment.
de Tisi J, Bell GS, Peacock JL, et al. The long-term outcome of adult epilepsy surgery, patterns of seizure remission, and relapse: a cohort study. Lancet. 2011;378(9800):1388-1395.
Sadek AR, Gray WP. Chopping and changing: long-term results of epilepsy surgery. Lancet. 2011;378(9800):1360-1362.

Biomarker Analysis and Volumetric MRI Strengthen Alzheimer’s Disease Predictions
Including CSF biomarker analysis and volumetric MRI in a patient’s work-up can greatly strengthen predictions of Alzheimer’s disease, researchers reported in the October 25 Neurology.

Although cognitive impairment, abnormal CSF biomarker levels, and medial temporal atrophy predict conversion from mild cognitive impairment (MCI) to Alzheimer’s disease, routine clinical work-ups focus only on the former risk factor, noted David S. Heister, MD, PhD, of the Department of Radiology at the University of California, San Diego, and colleagues. They investigated the ability of each factor, alone or in combination, to predict such a conversion within three years among 192 patients with MCI. The researchers used the Rey Auditory Verbal Learning Test to determine learning impairment and volumetric MRI to determine medial temporal atrophy.

The combined presence of any two of the three risk factors increased Alzheimer’s disease risk substantially, they found. A combination of learning impairment and medial temporal atrophy indicated the highest risk: 85% of patients with these factors, compared with 5% of patients with neither factor, were diagnosed with Alzheimer’s disease at three years. Furthermore, none of the 18 patients who tested negative for all of the risk factors, compared with 85% of the 55 patients who tested positive for all of the risk factors, developed Alzheimer’s disease. Of the risk factors, atrophy was associated with the worst median duration of dementia-free survival, at 25 months.

“The improved predictive prognostic information available from combined use of these measures argues strongly for their inclusion in the clinical investigation of suspected Alzheimer’s disease,” the researchers concluded. “Evidence of negative CSF or negative atrophy risk factors, with relatively intact learning ability, may allow a clinician to offer reassurance to patients with MCI that the likelihood of progressing to Alzheimer’s disease in the near term is small.… In contrast, a more aggressive course of treatment and care planning would be called for when either atrophy or CSF risk factors are present.”
Heister D, Brewer JB, Magda S, et al; the Alzheimer’s Disease Neuroimaging Initiative. Predicting MCI outcome with clinically available MRI and CSF biomarkers. Neurology. 2011;77(17):1619-1628.

Higher Doses of Vitamin D May Not Prevent More Lesions in Patients With MS
High doses of vitamin D2 showed no advantage compared with low doses of the vitamin in preventing or reducing brain lesions among patients with relapsing-remitting multiple sclerosis (MS), researchers reported in the October 25 Neurology.

Mark S. Stein, PhD, of Royal Melbourne Hospital, and colleagues performed a six-month randomized, controlled trial that included 23 patients with relapsing-remitting MS. Eleven patients were randomized to receive a high dose of vitamin D2 (6,000 IU), which was intended to elevate their serum 25-hydroxyvitamin D (250HD) to a level of 130 to 175 nM, while 12 patients were randomized to receive a placebo in place of the high dose. In addition, all patients received low doses of vitamin D2 (1,000 IU) to prevent deficiency.

During the follow-up period, patients underwent brain MRI and biochemical and clinical monitoring. The study’s primary end points were the cumulative number of new gadolinium-enhancing lesions and change in total volume of T2 lesions. Its secondary end points were scores on the Expanded Disability Status Scale (EDSS) and relapses.

After six months, the high-dose and low-dose groups did not differ significantly with regard to the development of new lesions or changes in the total volume of T2 lesions. Four patients who were in the high-dose group and two patients in the low-dose group developed new lesions, with totals of 14 new lesions in the high-dose group and 11 new lesions in the low-dose group. Patients in the high-dose group lost a median of 330 mm3 in lesion volume, and patients in the low-dose group lost a median of 95 mm3 of lesion volume.

Exit scores on the EDSS, after adjustment for entry scores on the scale, were marginally higher in the high-dose group than in the low-dose group. The median scores were 3 and 2 in the high-dose and low-dose groups, respectively. Four (36.5%) patients in the high-dose group and no patients in the low-dose group had a relapse.

It is possible that “any vitamin D benefit for MS occurs with low-level supplementation and oral vitamin D beyond that does not provide additional benefit,” the investigators speculated. “If this is the case, then epidemiologic correlations of better MS outcomes with higher serum 250HD may simply reflect the identification of people with MS who have a low probability of experiencing vitamin D deficiency.
Stein MS, Liu Y, Gray OM, et al. A randomized trial of high-dose vitamin D2 in relapsing-remitting multiple sclerosis. Neurology. 2011;77(17):1611-1618.

Epilepsy Surgery Reduces Seizures At 10 Years
One decade after undergoing epilepsy surgery, about half of patients remain free of all seizures except simple partial seizures (SPS), researchers reported iLiterature Monitorn the October 15 issue of Lancet.

Jane de Tisi, of the National Hospital for Neurology and Neurosurgery, London, and colleagues followed 615 adult patients for a median of eight years after epilepsy surgery. Of these patients, 497 had anterior temporal resection, 40 had temporal lesionectomy, 40 had extratemporal lesionectomy, 20 had extratemporal resection, 11 had hemispherectomy, and seven had a palliative procedure.

Freedom from non-SPS seizures occurred in 52% of patients at five years and 47% of patients at 10 years. Eighty-two percent of patients had at least one year of freedom from non-SPS seizures, and 73% of patients had at least one year of freedom from all seizures, including SPS.

Patients who experienced SPS within two years following surgery were twice as likely as other patients to experience subsequent seizures with impaired awareness. Relapse was less likely among patients with longer periods of seizure freedom, and remission was less likely among patients with longer periods of experiencing seizures. Seizure recurrence was twice as likely in patients with extratemporal resections as in patients with anterior temporal resections.

Late seizure remission was associated with the use of a previously unused antiepileptic drug in 18 (19%) of 93 patients who experienced such a remission following initial seizures or transient relapse. Of the 365 patients who were seizure-free at their latest follow-up, 104 (28%) had discontinued use of antiepileptic drugs.

“For seizure outcome, surgery is successful for many individuals in whom antiepileptic drugs have not been effective, but further improvements need to be made to presurgical assessment to further increase rates of success,” the investigators concluded. The predictive value of SPS following surgery “has implications for decisions to discontinue antiepileptic drugs in patients with only SPS,” added Ahmed-Ramadan Sadek, MD, and William Peter Gray, MD, both from the University of Southampton, UK, in an accompanying comment.
de Tisi J, Bell GS, Peacock JL, et al. The long-term outcome of adult epilepsy surgery, patterns of seizure remission, and relapse: a cohort study. Lancet. 2011;378(9800):1388-1395.
Sadek AR, Gray WP. Chopping and changing: long-term results of epilepsy surgery. Lancet. 2011;378(9800):1360-1362.

Biomarker Analysis and Volumetric MRI Strengthen Alzheimer’s Disease Predictions
Including CSF biomarker analysis and volumetric MRI in a patient’s work-up can greatly strengthen predictions of Alzheimer’s disease, researchers reported in the October 25 Neurology.

Although cognitive impairment, abnormal CSF biomarker levels, and medial temporal atrophy predict conversion from mild cognitive impairment (MCI) to Alzheimer’s disease, routine clinical work-ups focus only on the former risk factor, noted David S. Heister, MD, PhD, of the Department of Radiology at the University of California, San Diego, and colleagues. They investigated the ability of each factor, alone or in combination, to predict such a conversion within three years among 192 patients with MCI. The researchers used the Rey Auditory Verbal Learning Test to determine learning impairment and volumetric MRI to determine medial temporal atrophy.

The combined presence of any two of the three risk factors increased Alzheimer’s disease risk substantially, they found. A combination of learning impairment and medial temporal atrophy indicated the highest risk: 85% of patients with these factors, compared with 5% of patients with neither factor, were diagnosed with Alzheimer’s disease at three years. Furthermore, none of the 18 patients who tested negative for all of the risk factors, compared with 85% of the 55 patients who tested positive for all of the risk factors, developed Alzheimer’s disease. Of the risk factors, atrophy was associated with the worst median duration of dementia-free survival, at 25 months.

“The improved predictive prognostic information available from combined use of these measures argues strongly for their inclusion in the clinical investigation of suspected Alzheimer’s disease,” the researchers concluded. “Evidence of negative CSF or negative atrophy risk factors, with relatively intact learning ability, may allow a clinician to offer reassurance to patients with MCI that the likelihood of progressing to Alzheimer’s disease in the near term is small.… In contrast, a more aggressive course of treatment and care planning would be called for when either atrophy or CSF risk factors are present.”
Heister D, Brewer JB, Magda S, et al; the Alzheimer’s Disease Neuroimaging Initiative. Predicting MCI outcome with clinically available MRI and CSF biomarkers. Neurology. 2011;77(17):1619-1628.

Higher Doses of Vitamin D May Not Prevent More Lesions in Patients With MS
High doses of vitamin D2 showed no advantage compared with low doses of the vitamin in preventing or reducing brain lesions among patients with relapsing-remitting multiple sclerosis (MS), researchers reported in the October 25 Neurology.

Mark S. Stein, PhD, of Royal Melbourne Hospital, and colleagues performed a six-month randomized, controlled trial that included 23 patients with relapsing-remitting MS. Eleven patients were randomized to receive a high dose of vitamin D2 (6,000 IU), which was intended to elevate their serum 25-hydroxyvitamin D (250HD) to a level of 130 to 175 nM, while 12 patients were randomized to receive a placebo in place of the high dose. In addition, all patients received low doses of vitamin D2 (1,000 IU) to prevent deficiency.

During the follow-up period, patients underwent brain MRI and biochemical and clinical monitoring. The study’s primary end points were the cumulative number of new gadolinium-enhancing lesions and change in total volume of T2 lesions. Its secondary end points were scores on the Expanded Disability Status Scale (EDSS) and relapses.

After six months, the high-dose and low-dose groups did not differ significantly with regard to the development of new lesions or changes in the total volume of T2 lesions. Four patients who were in the high-dose group and two patients in the low-dose group developed new lesions, with totals of 14 new lesions in the high-dose group and 11 new lesions in the low-dose group. Patients in the high-dose group lost a median of 330 mm3 in lesion volume, and patients in the low-dose group lost a median of 95 mm3 of lesion volume.

Exit scores on the EDSS, after adjustment for entry scores on the scale, were marginally higher in the high-dose group than in the low-dose group. The median scores were 3 and 2 in the high-dose and low-dose groups, respectively. Four (36.5%) patients in the high-dose group and no patients in the low-dose group had a relapse.

It is possible that “any vitamin D benefit for MS occurs with low-level supplementation and oral vitamin D beyond that does not provide additional benefit,” the investigators speculated. “If this is the case, then epidemiologic correlations of better MS outcomes with higher serum 250HD may simply reflect the identification of people with MS who have a low probability of experiencing vitamin D deficiency.
Stein MS, Liu Y, Gray OM, et al. A randomized trial of high-dose vitamin D2 in relapsing-remitting multiple sclerosis. Neurology. 2011;77(17):1611-1618.

Epilepsy Surgery Reduces Seizures At 10 Years
One decade after undergoing epilepsy surgery, about half of patients remain free of all seizures except simple partial seizures (SPS), researchers reported iLiterature Monitorn the October 15 issue of Lancet.

Jane de Tisi, of the National Hospital for Neurology and Neurosurgery, London, and colleagues followed 615 adult patients for a median of eight years after epilepsy surgery. Of these patients, 497 had anterior temporal resection, 40 had temporal lesionectomy, 40 had extratemporal lesionectomy, 20 had extratemporal resection, 11 had hemispherectomy, and seven had a palliative procedure.

Freedom from non-SPS seizures occurred in 52% of patients at five years and 47% of patients at 10 years. Eighty-two percent of patients had at least one year of freedom from non-SPS seizures, and 73% of patients had at least one year of freedom from all seizures, including SPS.

Patients who experienced SPS within two years following surgery were twice as likely as other patients to experience subsequent seizures with impaired awareness. Relapse was less likely among patients with longer periods of seizure freedom, and remission was less likely among patients with longer periods of experiencing seizures. Seizure recurrence was twice as likely in patients with extratemporal resections as in patients with anterior temporal resections.

Late seizure remission was associated with the use of a previously unused antiepileptic drug in 18 (19%) of 93 patients who experienced such a remission following initial seizures or transient relapse. Of the 365 patients who were seizure-free at their latest follow-up, 104 (28%) had discontinued use of antiepileptic drugs.

“For seizure outcome, surgery is successful for many individuals in whom antiepileptic drugs have not been effective, but further improvements need to be made to presurgical assessment to further increase rates of success,” the investigators concluded. The predictive value of SPS following surgery “has implications for decisions to discontinue antiepileptic drugs in patients with only SPS,” added Ahmed-Ramadan Sadek, MD, and William Peter Gray, MD, both from the University of Southampton, UK, in an accompanying comment.
de Tisi J, Bell GS, Peacock JL, et al. The long-term outcome of adult epilepsy surgery, patterns of seizure remission, and relapse: a cohort study. Lancet. 2011;378(9800):1388-1395.
Sadek AR, Gray WP. Chopping and changing: long-term results of epilepsy surgery. Lancet. 2011;378(9800):1360-1362.

Biomarker Analysis and Volumetric MRI Strengthen Alzheimer’s Disease Predictions
Including CSF biomarker analysis and volumetric MRI in a patient’s work-up can greatly strengthen predictions of Alzheimer’s disease, researchers reported in the October 25 Neurology.

Although cognitive impairment, abnormal CSF biomarker levels, and medial temporal atrophy predict conversion from mild cognitive impairment (MCI) to Alzheimer’s disease, routine clinical work-ups focus only on the former risk factor, noted David S. Heister, MD, PhD, of the Department of Radiology at the University of California, San Diego, and colleagues. They investigated the ability of each factor, alone or in combination, to predict such a conversion within three years among 192 patients with MCI. The researchers used the Rey Auditory Verbal Learning Test to determine learning impairment and volumetric MRI to determine medial temporal atrophy.

The combined presence of any two of the three risk factors increased Alzheimer’s disease risk substantially, they found. A combination of learning impairment and medial temporal atrophy indicated the highest risk: 85% of patients with these factors, compared with 5% of patients with neither factor, were diagnosed with Alzheimer’s disease at three years. Furthermore, none of the 18 patients who tested negative for all of the risk factors, compared with 85% of the 55 patients who tested positive for all of the risk factors, developed Alzheimer’s disease. Of the risk factors, atrophy was associated with the worst median duration of dementia-free survival, at 25 months.

“The improved predictive prognostic information available from combined use of these measures argues strongly for their inclusion in the clinical investigation of suspected Alzheimer’s disease,” the researchers concluded. “Evidence of negative CSF or negative atrophy risk factors, with relatively intact learning ability, may allow a clinician to offer reassurance to patients with MCI that the likelihood of progressing to Alzheimer’s disease in the near term is small.… In contrast, a more aggressive course of treatment and care planning would be called for when either atrophy or CSF risk factors are present.”
Heister D, Brewer JB, Magda S, et al; the Alzheimer’s Disease Neuroimaging Initiative. Predicting MCI outcome with clinically available MRI and CSF biomarkers. Neurology. 2011;77(17):1619-1628.

Higher Doses of Vitamin D May Not Prevent More Lesions in Patients With MS
High doses of vitamin D2 showed no advantage compared with low doses of the vitamin in preventing or reducing brain lesions among patients with relapsing-remitting multiple sclerosis (MS), researchers reported in the October 25 Neurology.

Mark S. Stein, PhD, of Royal Melbourne Hospital, and colleagues performed a six-month randomized, controlled trial that included 23 patients with relapsing-remitting MS. Eleven patients were randomized to receive a high dose of vitamin D2 (6,000 IU), which was intended to elevate their serum 25-hydroxyvitamin D (250HD) to a level of 130 to 175 nM, while 12 patients were randomized to receive a placebo in place of the high dose. In addition, all patients received low doses of vitamin D2 (1,000 IU) to prevent deficiency.

During the follow-up period, patients underwent brain MRI and biochemical and clinical monitoring. The study’s primary end points were the cumulative number of new gadolinium-enhancing lesions and change in total volume of T2 lesions. Its secondary end points were scores on the Expanded Disability Status Scale (EDSS) and relapses.

After six months, the high-dose and low-dose groups did not differ significantly with regard to the development of new lesions or changes in the total volume of T2 lesions. Four patients who were in the high-dose group and two patients in the low-dose group developed new lesions, with totals of 14 new lesions in the high-dose group and 11 new lesions in the low-dose group. Patients in the high-dose group lost a median of 330 mm3 in lesion volume, and patients in the low-dose group lost a median of 95 mm3 of lesion volume.

Exit scores on the EDSS, after adjustment for entry scores on the scale, were marginally higher in the high-dose group than in the low-dose group. The median scores were 3 and 2 in the high-dose and low-dose groups, respectively. Four (36.5%) patients in the high-dose group and no patients in the low-dose group had a relapse.

It is possible that “any vitamin D benefit for MS occurs with low-level supplementation and oral vitamin D beyond that does not provide additional benefit,” the investigators speculated. “If this is the case, then epidemiologic correlations of better MS outcomes with higher serum 250HD may simply reflect the identification of people with MS who have a low probability of experiencing vitamin D deficiency.
Stein MS, Liu Y, Gray OM, et al. A randomized trial of high-dose vitamin D2 in relapsing-remitting multiple sclerosis. Neurology. 2011;77(17):1611-1618.