An enzyme-replacement therapy for the treatment of infantile-onset Pompe’s disease was proven safe and effective, reported researchers in the December 6 online issue of Neurology. Eighteen patients diagnosed with rapidly progressing Pompe’s disease before age 6 months were administered IV infusions of recombinant human acid α-glucosidase every other week, in either 20- or 40-mg/kg concentrations. Eleven patients experienced mild to moderate adverse effects; none discontinued treatment. All patients survived to age 18 months, and the investigators reported that, compared with historical no-treatment controls, risk of death was reduced by 99%; risk of death or any type of ventilation was reduced by 88%. No clear advantage was observed in the higher-dosage group.

Low to moderate blood alcohol concentrations (BACs) may have a beneficial effect on patients hospitalized for blunt head trauma, according to research published in the December Archives of Surgery. Investigators compared in-hospital death rates for 1,158 consecutive patients with severe brain injury from blunt head trauma. Nearly 30% of patients with low to moderate BAC died, significantly less than the mortality of those with no BAC and high BAC (36% and 45%, respectively). Compared with no BAC, the odds ratio for death was 0.76 for low to moderate BAC, though patients with high BAC (230 mg/dL or greater) had an increased odds ratio for death of 1.73. The authors concluded, “Alcohol-based fluids may have a role in the management of patients with severe brain injury after they have been well resuscitated.”

High doses of glycogen synthase kinase-3β−inhibiting drugs, previously speculated to be useful in treating Alzheimer’s disease, may impair neuronal function, according to a study published in the December 21 Neuron. Investigators reported that mouse neurons with a strong knockdown of GSK-3β expression displayed markedly reduced axon growth, and neurons with a mutant form of the enzyme were associated with defects in axon polarity. However, the researchers said that they corroborated previous evidence that moderate reduction of GSK-3β activity induced axon branching. They also utilized high and low doses of pharmacologic GSK-3β inhibitors and found that while high doses impaired neuronal function, low doses improved it. Further studies should focus on the effect of inhibiting GSK-3β in whole-mouse models, they added.

Impaired early brain development may be linked to the severity of spinocerebellar ataxia type 1 (SCA1) in adulthood. As reported in the November 17 Cell, researchers delayed expression of mutant Atxn1 known to cause SCA1 for two weeks in one group of mice, while controls had the active gene for the duration of the study.The investigators reported that they observed no signs of ataxia in the delayed-expression mice after 12 weeks, while the mice with the unsuppressed gene displayed moderate signs of ataxia; the delayed-expression mice also “performed markedly better” on accelerating treadmills than did the controls. The researchers further linked the mutant expression to decreases in RORα-mediated genes critical to cerebellar cell development and function.

People with low levels of LDL cholesterol are more likely to have Parkinson’s disease, as reported in Movement Disorders online December 18. Investigators recruited 124 Parkinson’s disease patients and 112 of their spouses. Compared with those with LDL cholesterol levels greater than 137 mg/dL, odds ratios for developing Parkinson’s disease were 2.6 for levels less than 93 mg/dL, 3.5 for levels between 93 and 114 mg/dL, and 2.2 for levels between 115 and 137 mg/dL. The researchers also noted that the use of either cholesterol-lowering drugs or statins alone was related to a lower occurrence of Parkinson’s disease. The authors suggested that low LDL cholesterol levels may increase, or that statin use may lower, the occurrence of Parkinson’s disease, and both hypotheses warrant further investigation.

Methamphetamine use may increase the risk of neck artery tears and subsequent stroke, according to a review of two cases in the December 26 Neurology. According to the authors, the report of severe stroke from carotid artery dissection following methamphetamine use yielded the first possible link between the two events. Neither patient had significant risk factors for stroke besides methamphetamine use, and results on head CT appeared normal in both patients, the authors stated. They noted that cocaine has effects similar to those of methamphetamine and has been implicated in aortic and carotid artery dissection; therefore, the tears may be due to a class drug effect rather than specific to methamphetamine use.

The prevalence of depressive symptoms in patients with multiple sclerosis (MS) may be high and can affect clinical management of the disease, reported researchers in the January Journal of Neurology, Neurosurgery, and Psychiatry. Of 166 persons with MS, 28 participants were depressed (Beck Depression Inventory [BDI] score greater than 12). Antidepressant treatment had been previously prescribed for 18 participants, of whom five were still depressed at the time of the interview. Depressive symptoms were equally common across disease severity, duration, and type; education level; living accommodation; and employment status. Depressed MS patients had worse functioning than nondepressed participants only in psychosocial categories; however, when the threshold for depression diagnosis was lowered (BDI score greater than 9), self-reported mobility and ambulation were also significantly worse.

Higher cumulative doses of lev­o­dopa and levodopa equivalents may be associated with the earlier occurrence of motor complications, according to research published in the December Archives of Neurology. Of 301 participants with early Parkinson’s disease, 189 developed motor complications during a four-year period: 38% of them developed motor fluctuations only, 12% developed dyskinesias only, and 50% developed both. In addition to the observed association between cumulative doses of le­vodopa or levo­dopa plus pramipexole and earlier onset of complications, the researchers reported that the development of motor fluctuations and dyskinesias were interrelated, as the presence of one was associated with the earlier development of the other. Hoehn and Yahr stage 2 or higher was also associated with earlier occurrence of dyskinesias, while pramipexole treatment was associated with the later occurrence of both motor complications.

Status epilepticus in patients with cancer may be responsive to therapy, as reported in the December Archives of Neurology. Investigators calculated a 23% 30-day mortality from 35 patients with status epilepticus secondary to a tumor or its treatment, and patients with systemic cancer had a higher risk of death (50% of patients with systemic cancer died within 30 days, compared with 14% of those with primary brain tumors). The authors said that overall survival correlated well with predicted survival from the underlying tumor. They recommended that brain imaging be performed on brain cancer patients with status epilepticus, even in the presence of subtherapeutic antiepileptic drug levels, because “status epilepticus usually occurs in the setting of tumor progression or new metastases.”

Persons with mild cognitive impairment (MCI) are likely to also have impaired motor function, and the degree of impairment in the lower extremities is related to the risk for Alzheimer’s disease, as reported in the December Archives of Neurology. Of 816 participants, 198 displayed MCI and 60 had Alzheimer’s disease. Researchers measured upper and lower extremity motor performance and observed that those with MCI had more combined motor impairment compared to those with no cognitive impairment, but less impairment than those with Alzheimer’s disease. In addition, within the MCI subgroup, participants with relatively poor lower extremity function (10th percentile) were 2.3 times more likely to develop Alzheimer’s disease than were those with good lower limb function (90th percentile). Upper extremity motor function was unrelated to risk of Alzheimer’s disease.

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