Objective: To determine the efficacy of medical marijuana in several neurologic conditions. Methods:We performed a systematic review of medical marijuana (1948( -November 2013 to address treatment of symptoms of multiple sclerosis (MS), epilepsy, and movement disorders. We graded the studies according to the American Academy of Neurology classification scheme for therapeutic articles.Results: Thirty-four studies met inclusion criteria; 8 were rated as Class I. Conclusions:The following were studied in patients with MS: (1) Spasticity: oral cannabis extract (OCE) is effective, and nabiximols and tetrahydrocannabinol (THC) are probably effective, for reducing patientcentered measures; it is possible both OCE and THC are effective for reducing both patient-centered and objective measures at 1 year. (2) Central pain or painful spasms (including spasticity-related pain, excluding neuropathic pain): OCE is effective; THC and nabiximols are probably effective. (3) Urinary dysfunction: nabiximols is probably effective for reducing bladder voids/day; THC and OCE are probably ineffective for reducing bladder complaints. (4) Tremor: THC and OCE are probably ineffective; nabiximols is possibly ineffective. (5) Other neurologic conditions: OCE is probably ineffective for treating levodopa-induced dyskinesias in patients with Parkinson disease. Oral cannabinoids are of unknown efficacy in non-chorea-related symptoms of Huntington disease, Tourette syndrome, cervical dystonia, and epilepsy. The risks and benefits of medical marijuana should be weighed carefully. Risk of serious adverse psychopathologic effects was nearly 1%. Comparative effectiveness of medical marijuana vs other therapies is unknown for these indications. Neurology ® 2014;82:1556-1563 GLOSSARY AAN 5 American Academy of Neurology; AE 5 adverse effect; CBD 5 cannabidiol; CI 5 confidence interval; CRS 5 category rating scale; HD 5 Huntington disease; ITT 5 intention-to-treat; MS 5 multiple sclerosis; NRS 5 numeric rating score; OCE 5 oral cannabis extract; THC 5 D-9-tetrahydrocannabinol; UHDRS 5 Unified Huntington's Disease Rating Scale; UPDRS 5 Unified Parkinson's Disease Rating Scale; VAS 5 visual analog scale.

Objective: To reassess the evidence for management issues related to the care of women with epilepsy (WWE) during pregnancy. Results: It is highly probable that intrauterine first-trimester valproate (VPA) exposure has higher risk of major congenital malformations (MCMs) compared to carbamazepine and possible compared to phenytoin or lamotrigine. Compared to untreated WWE, it is probable that VPA as part of polytherapy and possible that VPA as monotherapy contribute to the development of MCMs. It is probable that antiepileptic drug (AED) polytherapy as compared to monotherapy regimens contributes to the development of MCMs and to reduced cognitive outcomes. For monotherapy, intrauterine exposure to VPA probably reduces cognitive outcomes. Further, monotherapy exposure to phenytoin or phenobarbital possibly reduces cognitive outcomes. Neonates of WWE taking AEDs probably have an increased risk of being small for gestational age and possibly have an increased risk of a 1-minute Apgar score of Ͻ7. Methods: Recommendations:If possible, avoidance of valproate (VPA) and antiepileptic drug (AED) polytherapy during the first trimester of pregnancy should be considered to decrease the risk of major congenital malformations (Level B). If possible, avoidance of VPA and AED polytherapy throughout pregnancy should be considered to prevent reduced cognitive outcomes (Level B). If possible, avoidance of phenytoin and phenobarbital during pregnancy may be considered to prevent reduced cognitive outcomes (Level C). Pregnancy risk stratification should reflect that the offspring of women with epilepsy taking AEDs are probably at increased risk for being small for gestational age (Level B) and possibly at increased risk of 1-minute Apgar scores of Ͻ7 (Level C). Neurology ® 2009;73:133-141 GLOSSARY AAN ϭ Academy of Neurology; AED ϭ antiepileptic drug; CBZ ϭ carbamazepine; CI ϭ confidence interval; LTG ϭ lamotrigine; MCM ϭ major congenital malformation; OR ϭ odds ratio; PB ϭ phenobarbital; PHT ϭ phenytoin; RR ϭ relative risk; SGA ϭ small for gestational age; VPA ϭ valproate; WWE ϭ women with epilepsy.

Objective: To reassess the evidence for management issues related to the care of women with epilepsy (WWE) during pregnancy, including preconceptional folic acid use, prenatal vitamin K use, risk of hemorrhagic disease of the newborn, clinical implications of placental and breast milk transfer of antiepileptic drugs (AEDs), risks of breastfeeding, and change in AED levels during pregnancy. Results: Preconceptional folic acid supplementation is possibly effective in preventing major congenital malformations in the newborns of WWE taking AEDs. There is inadequate evidence to determine if the newborns of WWE taking AEDs have a substantially increased risk of hemorrhagic complications. Primidone and levetiracetam probably transfer into breast milk in amounts that may be clinically important. Valproate, phenobarbital, phenytoin, and carbamazepine probably are not transferred into breast milk in clinically important amounts. Pregnancy probably causes an increase in the clearance and a decrease in the concentration of lamotrigine, phenytoin, and to a lesser extent carbamazepine, and possibly decreases the level of levetiracetam and the active oxcarbazepine metabolite, the monohydroxy derivative. Methods:Recommendations: Supplementing women with epilepsy with at least 0.4 mg of folic acid before they become pregnant may be considered (Level C). Monitoring of lamotrigine, carbamazepine, and phenytoin levels during pregnancy should be considered (Level B) and monitoring of levetiracetam and oxcarbazepine (as monohydroxy derivative) levels may be considered (Level C). A paucity of evidence limited the strength of many recommendations. Neurology ® 2009;73:142-149 GLOSSARY AAN ϭ American Academy of Neurology; AED ϭ antiepileptic drug; CBZ ϭ carbamazepine; CI ϭ confidence interval; ESM ϭ ethosuximide; GBP ϭ gabapentin; LTG ϭ lamotrigine; LVT ϭ levetiracetam; MHD ϭ monohydroxy derivative; OR ϭ odds ratio; OXC ϭ oxcarbazepine; PB ϭ phenobarbital; PHT ϭ phenytoin; PRM ϭ primidone; TPM ϭ topiramate; VPA ϭ valproate; WWE ϭ women with epilepsy.

SUMMARYA committee assembled by the American Academy of Neurology (AAN) reassessed the evidence related to the care of women with epilepsy (WWE) during pregnancy, including antiepileptic drug (AED) teratogenicity and adverse perinatal outcomes. It is highly probable that intrauterine first-trimester valproate (VPA) exposure has higher risk of major congenital malformations (MCMs) compared to carbamazepine (CBZ), and possibly compared to phenytoin (PHT) or lamotrigine (LTG). It is probable that VPA as part of polytherapy and possible that VPA as monotherapy contribute to the development of MCMs. AED polytherapy probably contributes to the development of MCMs and reduced cognitive outcomes compared to monotherapy. Intrauterine exposure to VPA monotherapy probably reduces cognitive outcomes and monotherapy exposure to PHT or phenobarbital (PB) possibly reduces cognitive outcomes. Neonates of WWE taking AEDs probably have an increased risk of being small for gestational age and possibly have an increased risk of a 1-minute Apgar score of <7. If possible, avoidance of VPA and AED polytherapy during the first trimester of pregnancy should be considered to decrease the risk of MCMs. If possible, avoidance of VPA and AED polytherapy throughout pregnancy should be considered and avoidance of PHT and PB throughout pregnancy may be considered to prevent reduced cognitive outcomes.

ILInterleukin CD Cluster of differentiation INF Interferon SSPE Subacute sclerosing panencephalitis Subacute sclerosing panencephalitis (SSPE) is a chronic encephalitis occurring after infection with measles virus. The prevalence of the disease varies depending on uptake of measles vaccination, with the virus disproportionally affecting regions with low vaccination rates. The physiopathology of the disease is not fully understood; however, there is evidence that it involves factors that favour humoral over cellular immune response against the virus. As a result, the virus is able to infect the neurons and to survive in a latent form for years. The clinical manifestations occur, on average, 6 years after measles virus infection. The onset of SSPE is insidious, and psychiatric manifestations are prominent. Subsequently, myoclonic seizures usually lead to a final stage of akinetic mutism. The diagnosis is clinical, supported by periodic complexes on electroencephalography, brain imaging suggestive of demyelination, and immunological evidence of measles infection. Management of the disease includes seizure control and avoidance of secondary complications associated with the progressive disability. Trials of treatment with interferon, ribavirin, and isoprinosine using different methodologies have reported beneficial results. However, the disease shows relentless progression; only 5% of individuals with SSPE undergo spontaneous remission, with the remaining 95% dying within 5 years of diagnosis.

Objective: To reassess the evidence for management issues related to the care of women with epilepsy (WWE) during pregnancy, including the risk of pregnancy complications or other medical problems during pregnancy in WWE compared to other women, change in seizure frequency, the risk of status epilepticus, and the rate of remaining seizure-free during pregnancy.Methods: A 20-member committee including general neurologists, epileptologists, and doctors in pharmacy evaluated the available evidence based on a structured literature review and classification of relevant articles published between 1985 and February 2008. Results: For WWE taking antiepileptic drugs, there is probably no substantially increased risk (greater than two times expected) of cesarean delivery or late pregnancy bleeding, and probably no moderately increased risk (greater than 1.5 times expected) of premature contractions or premature labor and delivery. There is possibly a substantially increased risk of premature contractions and premature labor and delivery during pregnancy for WWE who smoke. Seizure freedom for at least 9 months prior to pregnancy is probably associated with a high likelihood (84%-92%) of remaining seizure-free during pregnancy. Recommendations:Women with epilepsy (WWE) should be counseled that seizure freedom for at least 9 months prior to pregnancy is probably associated with a high rate (84%-92%) of remaining seizure-free during pregnancy (Level B). However, WWE who smoke should be counseled that they possibly have a substantially increased risk of premature contractions and premature labor and delivery during pregnancy (Level C). Neurology Recent estimates of the US population 1 and the prevalence of epilepsy 2 indicate that approximately one-half million women with epilepsy (WWE) are of childbearing age. It has also been estimated that three to five births per thousand will be to WWE.3 Epilepsy is defined by the presence of recurrent, unprovoked seizures, and the treatment is typically a daily, long-term antiepileptic drug (AED) regimen. The majority of people with epilepsy have well-controlled seizures, are otherwise healthy, and therefore expect to participate fully in life experiences, including childbearing.This parameter and the two companion parameters are updates of the previous practice parameter from 1998. The arbitrary cutoff date of 1985 was chosen because these relatively recent articles were thought to reflect current practice and AED usage patterns and therefore be more applicable and reliable for this assessment than earlier reports. The search terms used were seizures/epilepsy, catamenial epilepsy, pregnancy, anticonvulsants, antiepileptic drugs, teratogenesis, birth defects, pregnancy registry, cognitive outcome, vitamin K, folate/folic acid, breastfeeding, oral contraceptives, polycystic ovary syndrome, hormone replacement therapy, menopause, perimenopause, and fertility. The search was confined to articles using human subjects and included all languages for which there was an abstract in En...

SUMMARYA committee assembled by the American Academy of Neurology (AAN) reassessed the evidence related to the care of women with epilepsy (WWE) during pregnancy, including preconceptional folic acid and prenatal vitamin K use and the clinical implications of placental and breast-milk transfer of antiepileptic drugs (AEDs). The committee evaluated the available evidence based on a structured literature review and classification of relevant articles. Preconceptional folic acid supplementation is possibly effective in preventing major congenital malformations in the newborns of WWE taking AEDs. There is inadequate evidence to determine if the newborns of WWE taking AEDs have a substantially increased risk of hemorrhagic complications. Primidone and levetiracetam probably transfer into breast milk in clinically important amounts. Valproate, phenobarbital, phenytoin, and carbamazepine probably are not transferred into breast milk in clinically important amounts. Pregnancy probably causes an increase in the clearance and a decrease in the concentrations of lamotrigine, phenytoin, and, to a lesser extent carbamazepine, and possibly decreases the level of levetiracetam and the active oxcarbazepine metabolite, the monohydroxy derivative (MHD). Supplementing WWE with at least 0.4 mg of folic acid before pregnancy may be considered. Monitoring of lamotrigine, carbamazepine, and phenytoin levels during pregnancy should be considered, and monitoring of

SUMMARYA committee assembled by the American Academy of Neurology (AAN) reassessed the evidence related to the care of women with epilepsy (WWE) during pregnancy, including the risk of pregnancy complications or other medical problems during pregnancy, change in seizure frequency, the risk of status epilepticus, and the rate of remaining seizure-free during pregnancy. The committee evaluated the available evidence according to a structured literature review and classification of relevant articles. For WWE who are taking antiepileptic drugs (AEDs), there is probably no substantially increased risk (>2 times expected) of cesarean delivery or late pregnancy bleeding, and probably no moderately increased risk (>1.5 times expected) of premature contractions or premature labor and delivery. There is possibly a substantially increased risk of premature contractions and premature labor and delivery during pregnancy for WWE who smoke. WWE should be counseled that seizure freedom for at least 9 months prior to pregnancy is probably associated with a high likelihood (84-92%) of remaining seizure-free during pregnancy. WWE who smoke should be counseled that they possibly have a substantially increased risk of premature contractions and premature labor and delivery. KEY WORDS: Guideline, Pregnancy, Epilepsy, Seizure, Complications. This article is being published jointly/simultaneously by ILAE in Epilepsia and AAN in Neurology. Recent estimates of the U.S. population (United StatesDepartmentWiley Periodicals, Inc. ª 2009 International League Against Epilepsy Epilepsia, 50(5): 1229-1236, 2009 doi: 10.1111/j.1528-1167.2009.02128.x SPECIAL REPORT1229 approximately one-half million women with epilepsy (WWE) are of childbearing age. It has also been estimated that 3-5 births per thousand will be to WWE (Yerby, 2000). Epilepsy is defined by the presence of recurrent, unprovoked seizures, and the treatment is typically a daily, long-term antiepileptic drug (AED) regimen. The majority of people with epilepsy have well-controlled seizures, are otherwise healthy, and, therefore, expect to participate fully in life experiences, including child-bearing.This parameter and the two companion parameters are updates of the previous practice parameter from 1998 (American Academy of Neurology, 1998). They employ improved methodology for the development of practice parameters to analyze a large number of new studies informing the clinical management of WWE who are pregnant or plan pregnancy.This parameter summarizes evidence for two broad clinical questions:Compared to women without epilepsy, are WWE at increased risk for pregnancy-related complications, including (1) cesarean delivery; (2) preeclampsia; (3) pregnancy-induced hypertension; (4) premature contractions or premature labor and delivery; (5) bleeding complications; and (6) spontaneous abortion?For WWE who become pregnant, what is the risk of epilepsy-related complications during pregnancy, including (1) change in seizure frequency, (2) risk of status epilepticus, and (3) chance...