Practice parameter update: evaluation and management of driving risk in dementia: report of the Quality Standards Subcommittee of the American Academy of Neurology.

OBJECTIVE: To review the evidence regarding the usefulness of patient demographic characteristics, driving history, and cognitive testing in predicting driving capability among patients with dementia and to determine the efficacy of driving risk reduction strategies. METHODS: Systematic review of the literature using the American Academy of Neurology's evidence-based methods. RECOMMENDATIONS: For patients with dementia, consider the following characteristics useful for identifying patients at increased risk for unsafe driving: the Clinical Dementia Rating scale (Level A), a caregiver's rating of a patient's driving ability as marginal or unsafe (Level B), a history of crashes or traffic citations (Level C), reduced driving mileage or self-reported situational avoidance (Level C), Mini-Mental State Examination scores of 24 or less (Level C), and aggressive or impulsive personality characteristics (Level C). Consider the following characteristics not useful for identifying patients at increased risk for unsafe driving: a patient's self-rating of safe driving ability (Level A) and lack of situational avoidance (Level C). There is insufficient evidence to support or refute the benefit of neuropsychological testing, after controlling for the presence and severity of dementia, or interventional strategies for drivers with dementia (Level U).

Reassessment: neuroimaging in the emergency patient presenting with seizure (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

OBJECTIVE: To reassess the value of neuroimaging of the emergency patient presenting with seizure as a screening procedure for providing information that will change acute management, and to reassess clinical and historical features associated with an abnormal neuroimaging study in these patients. METHODS: A broad-based panel with topic expertise evaluated the available evidence based on a structured literature review using a Medline search from 1966 until November 2004. RESULTS: The 15 articles meeting criteria were Class II or III evidence since interpretation was not masked to the patient's clinical presentation; most were series including 22 to 875 patients. There is evidence that for adults with first seizure, cranial CT will change acute management in 9 to 17% of patients. CT in the emergency department for children presenting with first seizure will change acute management in approximately 3 to 8%. There is no clear difference between rates of abnormal emergent CT for patients with chronic seizures vs first. Children <6 months presenting with seizures have clinically relevant abnormalities on CT scans 50% of the time. Persons with AIDS and first seizure have high rates of abnormalities, and CNS toxoplasmosis is frequently found. Abnormal neurologic examination, predisposing history, or focal seizure onset are probably predictive of an abnormal CT study in this context. CONCLUSIONS: Immediate noncontrast CT is possibly useful for emergency patients presenting with seizure to guide appropriate acute management especially where there is an abnormal neurologic examination, predisposing history, or focal seizure onset.

Practice parameter: treatment of postherpetic neuralgia: an evidence-based report of the Quality Standards Subcommittee of the American Academy of Neurology.

A systematic review of the literature on postherpetic neuralgia was performed. The authors identified studies using the National Library of Medicine's Medline database and Cochrane Library database. The authors determined absolute reduction rate, number needed to treat (NNT), 95% CI for NNT, and number needed to harm (NNH) for successful therapies of postherpetic neuralgia. Tricyclic antidepressants, gabapentin, pregabalin, opioids, and lidocaine patch were found to be effective in reducing the pain of postherpetic neuralgia.

A randomized, double masked, controlled trial of botulinum toxin type A in essential hand tremor.

OBJECTIVE: To evaluate the safety and efficacy of botulinum toxin type A injection in essential tremor of the hand. BACKGROUND: Botulinum toxin type A is an effective treatment for dystonia, spasticity, and other movement disorders and has been found to be useful in open-label studies and one double-masked study of essential hand tremor. METHODS: One hundred thirty-three patients with essential tremor were randomized to low-dose (50 U) or high-dose (100 U) botulinum toxin type A (Botox) or vehicle placebo treatment. Injections were made into the wrist flexors and extensors. Patients were followed for 16 weeks. The effect of treatment was assessed by clinical rating scales, measures of motor tasks and functional disability, and global assessment of treatment. Hand strength was evaluated by clinical rating and by a dynamometer. RESULTS: Both doses of botulinum toxin type A significantly reduced postural tremor on the clinical rating scales after 4 to 16 weeks. However, kinetic tremor was significantly reduced only at the 6-week examination. Measures of motor tasks and functional disability were not consistently improved with botulinum toxin type A treatment. Grip strength was reduced for the low- and high-dose botulinum toxin type A groups as compared with the placebo group. Adverse reactions consisted mainly of dose-dependent hand weakness. CONCLUSION: Botulinum toxin type A injections for essential tremor of the hands resulted in significant improvement of postural, but not kinetic, hand tremors and resulted in limited functional efficacy. Hand weakness is a dose-dependent significant side effect of treatment at the doses used in this study.

Practice parameter: management of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology.

OBJECTIVE: To define and investigate key issues in the management of dementia and to make literature-based treatment recommendations. METHODS: The authors searched the literature for four clinical questions: 1) Does pharmacotherapy for cognitive symptoms improve outcomes in patients with dementia? 2) Does pharmacotherapy for noncognitive symptoms improve outcomes in patients with dementia? 3) Do educational interventions improve outcomes in patients and/or caregivers? 4) Do other nonpharmacologic interventions improve outcomes in patients and/or caregivers? RESULTS: Cholinesterase inhibitors benefit patients with AD (Standard), although the average benefit appears small; vitamin E likely delays the time to clinical worsening (Guideline); selegiline, other antioxidants, anti-inflammatories, and estrogen require further study. Antipsychotics are effective for agitation or psychosis in patients with dementia where environmental manipulation fails (Standard), and antidepressants are effective in depressed patients with dementia (Guideline). Educational programs should be offered to family caregivers to improve caregiver satisfaction and to delay the time to nursing home placement (Guideline). Staff of long-term care facilities should also be educated about AD to minimize the unnecessary use of antipsychotic medications (Guideline). Behavior modification, scheduled toileting, and prompted voiding reduce urinary incontinence (Standard). Functional independence can be increased by graded assistance, skills practice, and positive reinforcement (Guideline).

Practice parameter: risk of driving and Alzheimer's disease (an evidence-based review): report of the quality standards subcommittee of the American Academy of Neurology.

Studies of automobile accident frequency among drivers with AD have yielded conflicting results about the risk of accidents. To develop a practice parameter regarding driving and AD the authors performed a systematic review of the literature. The authors identified well-designed, controlled studies of driving and AD using the National Library of Medicine's MEDLINE database. The authors also compared the relative rates of crashes and other performance measurements of driving ability in the populations studied. Driving was found to be mildly impaired in those drivers with probable AD at a severity of Clinical Dementia Rating (CDR) 0.5. This impairment was no greater than that tolerated in other segments of the driving population (e.g., drivers age 16 to 21 and those driving under the influence of alcohol at a blood alcohol concentration [BAC] < 0.08%). Drivers with AD at a severity of CDR 1 were found to pose a significant traffic safety problem both from crashes and from driving performance measurements.

Botulinum toxin treatment of essential head tremor.

We examined in a double-blind, placebo-controlled study the effects of botulinum toxin in 10 patients with essential head tremor. Each subject received two treatments approximately 3 months apart, one with botulinum toxin injections and another with normal saline injections into the sternocleidomastoid and splenius capitis muscles. The subjects were assessed before each treatment and at 2, 4, and 8 weeks after injections. There was moderate to marked improvement in clinical ratings in five subjects after botulinum toxin injections and in one subject after placebo. There was moderate to marked subjective improvement in five patients with botulinum toxin as compared with three subjects with placebo. Side effects were mild and transient. We conclude that botulinum toxin may be useful for patients with essential head tremor who have failed to benefit from oral medications.

Comparison of glucose metabolism and cerebral blood flow during cortical motor activation.

Regions of cerebral cortex activated in normal subjects making simple, repetitive, voluntary wrist movements were studied with positron emission tomography (PET). The regional cerebral metabolic rate of glucose utilization was studied with 2-[18F]fluoro-2-deoxy-D-glucose (FDG), and regional cerebral blood flow was studied with 15O-labeled water. No significant activation was found with the cerebral metabolic rate studies. Studies of regional cerebral blood flow showed significant activation of the contralateral sensorimotor cortex region of 42%, of the ipsilateral sensorimotor cortex region of 19%, and of the medial frontal cortex of 30% compared with the resting state. Increases in blood flow in the contralateral sensorimotor cortex and medial frontal cortex were visible on every activated scan. Measurement of regional cerebral blood flow seems to be more sensitive than regional cerebral metabolic rate of glucose utilization for studying cortical activation with voluntary movement.

Essential tremor and dystonia.

We reviewed the database of the Dystonia Clinic at the University of Kansas Medical Center for patients with dystonia and tremor. Of 296 patients with idiopathic dystonia, 24 had dystonic tremor, 20 with cervical dystonia had an isolated head-nodding tremor, two patients with writer's cramp had ipsilateral hand tremor, and two patients with generalized dystonia had arm tremor. Eight patients, all with cervical dystonia, had essential tremor that preceded the onset of their dystonia.

Glucose metabolism in the brain of patients with essential tremor.

Using positron emission tomography with [18F]fluoro-2-deoxyglucose, we determined the regional cerebral metabolic rate of glucose utilization at rest in 8 medication-free patients with essential tremor and in 10 normal subjects. Taking the metabolic values of regions of interest as ratios to the mean hemispheric metabolism, the patients showed significant glucose hypermetabolism of the medulla and thalami, but not of the cerebellar cortex. This study lends support to earlier suggestions that circuits involving the inferior olivary nuclei in the medulla and the thalmus are involved in the generation of essential tremor.

Driving in Alzheimer's disease.

OBJECTIVE: To determine if the impaired mental skills in Alzheimer's Disease (AD) may adversely affect driving ability. DESIGN: Retrospective survey. SETTING: The Alzheimer's Clinic of the University of Kansas Medical Center. PATIENTS: We interviewed 67 AD patients and their families and compared them with 100 elderly, non-spousal controls. MEASURES: The questionnaire was designed to obtain information on their driving habits, with emphasis placed on whether they were still driving, and the number of accidents per year for the past 10 years. RESULTS: Forty-six of the AD subjects had stopped driving because of safety concerns expressed by the subjects, their families, or health care providers, and two had stopped for other reasons. Only two of the normal controls had stopped driving (P < 0.0001, Chi-square test). Over the past 3 years, the 19 AD subjects who were still driving had 263.2 motor vehicle accidents per million vehicle miles of travel compared with 14.3 for the controls (P < 0.002, Mann-Whitney U test) and 5.7 for the general driving population age > or = 55 years (P < 0.05, Students one group, two-tailed t test). CONCLUSION: This study suggests that a significant traffic safety problem exists in subjects with AD who continue to drive. Efforts should be directed to detect patients with AD whose driving presents a traffic safety problem.

Electromyographic guidance of botulinum toxin treatment in cervical dystonia.

We report the results of electromyographic (EMG) guidance in the treatment of cervical dystonia with botulinum toxin. Eight-four patients received a total of 225 injection sessions. Overall there was moderate objective improvement in 78.7%. The mean dose of toxin was 269 +/- 39 mouse lethal units and the mean duration of maximum effect was 107 +/- 49 days. Complications included excessive neck weakness in 16.0% and dysphagia in 11.1% of the injection sessions. We conclude that EMG guidance is a safe and effective method of administering botulinum toxin in the treatment of cervical dystonia.

Driving in Parkinson's disease.

Altered motor or mental skills in Parkinson's disease (PD) could adversely affect driving ability. We interviewed 150 patients regarding their driving habits and compared them with 100 controls. Thirty patients had stopped driving because of PD. PD patients had no more lifetime accidents than controls. With increased disability, however, there was a smaller percentage of patients still driving with fewer miles traveled and with proportionately more accidents occurring. Though disability scores did not correlate well with driving ability, there were significantly more accidents in subjects with more severe PD. The presence of cognitive impairment was associated with an increased accident rate. We conclude that driving in PD may be a public health problem and that some PD patients should not drive.

Increased glucose metabolism in the medulla of patients with palatal myoclonus.

Hypertrophic degeneration of the inferior olivary nuclei is the pathologic substrate for palatal myoclonus, but the physiologic correlate of this finding is uncertain. Using the 2-[18F]fluoro-2-deoxy-D-glucose and PET method, we determined the local cerebral metabolic rate of glucose utilization in seven patients with palatal myoclonus (following stroke or infection, or idiopathic), one patient with oculopalatal myoclonus (following a stroke affecting the brainstem), and nine normal subjects. The metabolism of glucose in the medulla of the patients with palatal myoclonus was significantly greater than that of the normal subjects. This may well have been due to increased metabolism of the inferior olivary nuclei. Glucose metabolism in the medulla of the patient with oculopalatal myoclonus was normal. These findings suggest that the inferior olivary nuclei, or a region of the brainstem encompassing the inferior olivary nuclei, are hypermetabolic in palatal myoclonus and may be the generators of the involuntary movements in palatal myoclonus.

Computed tomography, magnetic resonance imaging and positron emission tomography with [18F]fluorodeoxyglucose in multiple system atrophy and pure autonomic failure.

We studied 45 patients who had autonomic failure with computed tomography, magnetic resonance imaging and positron emission tomography with [18F]fluorodeoxyglucose to characterize the neuroimaging features of multiple system atrophy and pure autonomic failure and determine the utility of these techniques in distinguishing multiple system atrophy from pure autonomic failure. There were 30 patients with multiple system atrophy and 15 with pure autonomic failure. In the multiple system atrophy group, eight patients had mainly cerebellar signs, seven extrapyramidal and 15 had combinations of cerebellar and extrapyramidal signs. Cerebellar atrophy on computerized tomography and magnetic resonance imaging, signal hypointensity in the posterolateral putamen on magnetic resonance imaging and a generalized reduction in glucose utilization rate with positron emission tomography with [18F]fluorodeoxyglucose, were the main findings and were seen only in the patients with multiple system atrophy. Decreased glucose utilization (hypometabolism) was most prominent in the cerebellum, brainstem, striatum and frontal and motor cortices. These results indicate clear differences, using neuroimaging studies, between multiple system atrophy and pure autonomic failure.

Congenital mirror movements. Abnormal organization of motor pathways in two patients.

We studied 2 patients with congenital mirror movements by means of various neurophysiological and metabolic techniques, including mapping of motor evoked potentials to transcranial electrical and magnetic stimulation, premovement and somatosensory evoked potentials, kinematics of voluntary movements, muscle reflexes, and positron emission tomography (PET). Abnormalities in maps of motor and premovement potentials and in PET scans were consistent with a bilateral representation of hand muscles in the motor cortex, the existence of physiologically active connections capable of conducting fast efferent volleys from the motor cortex to ipsilateral muscles, the presence of mirror EMG activity in either hand with intended voluntary movement of the other hand, the absence of mirrored EMG responses from wrist flexors and extensors to mechanical perturbation of the contralateral wrist, and normal scalp distribution of somatosensory evoked potentials to right and left median nerve stimulation. Our findings are consistent with aberrant organization of motor representation areas and corticospinal pathways with ipsilateral as well as contralateral control of voluntary movement.

A double-blind trial of isoniazid for essential tremor and other action tremors.

We conducted a double-blind trial of isoniazid in 11 patients with essential tremor and four patients with other types of postural action tremor. The tremor had not been helped by beta-blockers or primidone. Isoniazid was given in doses up to 1,200 mg daily, together with 100 mg pyridoxine, for four weeks. Results were assessed with subjective and objective scales. Only two patients with essential tremor appeared to benefit enough to continue the drug after the trial, and only one has benefited from its long-term use. Isoniazid may be useful in rare cases of essential tremor, but must be monitored carefully because of its toxicity.

Reversible axonal neuropathy from the treatment of AIDS and related disorders with 2',3'-dideoxycytidine (ddC).

A total of 20 patients with acquired immune deficiency syndrome (AIDS) or AIDS-related complex (ARC) received the anti-retroviral drug 2',3',dideoxycytidine in a phase I study at doses ranging from 0.03 mg/kg every 8 hours to 0.25 mg/kg every 8 hours. Of the 11 patients who participated in the study for more than 5 weeks, 9 developed symptoms and signs of a mainly sensory painful neuropathy that was confirmed by electromyography to be mixed sensory and motor neuropathy of axonal type. The neuropathy which developed on dideoxycytidine occurred between 9 and 12 weeks of treatment. One patient, who had the drug stopped at 3 weeks owing to thrombocytopenia, developed a similar clinical picture of a sensory peripheral neuropathy after 2 weeks off dideoxycytidine. However, he did not have electromyographic evidence of a neuropathy, and he subsequently returned to normal clinically while taking a lower dose of dideoxycytidine in an alternating regimen. Five patients were withdrawn from the study because of the neuropathy. The pattern of this neuropathy was different from that of the slowly progressive painful neuropathy of AIDS, in that there was (1) a sudden onset of intense burning discomfort in both feet sparing the hands at about the tenth week (mean 10.4 weeks) of treatment, (2) there was motor involvement in some patients without progression, and (3) onset of the neuropathy was temporally related to the administration of dideoxycytidine and began to resolve 3-5 weeks after its discontinuation. We believe that dideoxycytidine can be an axonal toxin, especially when given in high dose continuous regimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Regional brain glucose metabolism in neuroacanthocytosis.

Two brothers with neuroacanthocytosis had [18F]-2-fluoro-2-deoxyglucose PET scans showing marked glucose hypometabolism of the caudate and putamen. MRIs showed no evidence of atrophy or modification of signal intensity in these structures. Decreased glucose utilization of the striatum can underlie hyperkinetic movement disorders of various etiologies.