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).

Assessment: Botulinum neurotoxin for the treatment of movement disorders (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

OBJECTIVE: To perform an evidence-based review of the safety and efficacy of botulinum neurotoxin (BoNT) in the treatment of movement disorders. METHODS: A literature search was performed including MEDLINE and Current Contents for therapeutic articles relevant to BoNT and selected movement disorders. Authors reviewed, abstracted, and classified articles based on American Academy of Neurology criteria (Class I-IV). RESULTS: The highest quality literature available for the respective indications was as follows: blepharospasm (two Class II studies); hemifacial spasm (one Class II and one Class III study); cervical dystonia (seven Class I studies); focal upper extremity dystonia (one Class I and three Class II studies); focal lower extremity dystonia (one Class II study); laryngeal dystonia (one Class I study); motor tics (one Class II study); and upper extremity essential tremor (two Class II studies). RECOMMENDATIONS: Botulinum neurotoxin should be offered as a treatment option for the treatment of cervical dystonia (Level A), may be offered for blepharospasm, focal upper extremity dystonia, adductor laryngeal dystonia, and upper extremity essential tremor (Level B), and may be considered for hemifacial spasm, focal lower limb dystonia, and motor tics (Level C). While clinicians' practice may suggest stronger recommendations in some of these indications, evidence-based conclusions are limited by the availability of data.

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).

Modified order of allelic replication in lymphoma patients at different disease stages.

Asynchronous replication of homologous loci was reported in lymphocytes of patients with lymphoma, ovarian and renal cancer as well as in lymphocytes of patients with premalignant conditions, for example, essential mixed cryoglobulinemia associated with hepatitis C virus and in monoclonal gammopathy of unknown significance. In the present study we evaluated the replication pattern in lymphocytes of four groups of patients with intermediate grade of non-Hodgkin lymphoma at various stages of their disease: 1) at diagnosis; 2) during cytotoxic treatment; 3) in remission; and 4) in relapse. A significantly higher proportion of the asynchronous pattern of replication at diagnosis, during cytotoxic treatment, and in relapse was noted as compared to healthy controls and to patients who achieved remission of their lymphoma. Also, the frequency of the two doublets (DD) pattern in every group studied was significantly lower than in the controls. If our findings can be confirmed in larger, long-term prospective studies, it may allow the use of a simple and inexpensive tool to closely observe patients with lymphoma who are at high risk for relapse.

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.

Early morning akinesia in Parkinson's disease: effect of standard carbidopa/levodopa and sustained-release carbidopa/levodopa.

We examined the effects of supplemental standard carbidopa/levodopa (Std-L) on early morning akinesia in patients with Parkinson's disease (PD) who were being treated with sustained-release carbidopa/levodopa (L-CR). We compared plasma dopa levels and clinical response in 15 PD patients after a dose of Std-L and L-CR (2 hours later) and after a dose of L-CR and placebo in a double-blind, placebo-controlled, crossover study. Plasma dopa levels, total motor score, walking time, and finger tapping time were assessed every 15 minutes for the first 2 hours and then every 30 minutes for the next 3 hours. The time of onset in clinical benefit was significantly earlier with Std-L (47 minutes, range 15 to 75 minutes) as the first dose as compared with L-CR (58 minutes, range 30 to 105 minutes). Similarly, there was a significant difference in the peak plasma dopa levels (Cmax) and the time to reach peak plasma dopa levels (Tmax) with administration of Std-L (Tmax 36 minutes; Cmax 1,501 micrograms/ml) as compared with L-CR (Tmax 111 minutes, Cmax 1,260 micrograms/ml). There was no significant difference in dyskinesias between the two treatment arms. An initial morning dose of Std-L alleviates the problem of delayed-onset clinical response that commonly occurs with L-CR.

Fluorescence in situ hybridization (FISH) for retrospective detection of trisomies 3 and 7 in multiple myeloma.

The malignant plasma cells of multiple myeloma (MM) have a low proliferative activity and therefore cytogenetic studies of the disease have been severely limited. We evaluated the role of fluorescence in situ hybridization (FISH) in the detection of numerical chromosomal abnormalities in early stages of myeloma and the applicability of the method to stored archival slides. Old air-dried bone marrow smears from 15 myeloma patients obtained at presentation were probed with alpha satellite DNA sequences to chromosomes 3 and 7. Numerical chromosome aberrations were found in eight (53%) of the patients, including six (of 12) with trisomy 7, and two (of eight) with trisomy 3. This study demonstrates that FISH is a sensitive method for the detection of numerical aberrations in myeloma and for the study of old slides for retrospective analysis.

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.

Classification of essential tremor.

Classification of essential tremor was attempted using tremor frequency; tremor duration; family history of tremor; responsiveness to alcohol, propranolol, and primidone; muscle contraction pattern; and long-latency reflexes. Sixty-one patients were evaluated. The majority of patients had a tremor frequency less than 7.0 Hz, a positive family history, and a positive response to alcohol. Approximately 46% of patients had a beneficial response with propranolol and 71% with primidone. Tremor frequency was inversely correlated with age and directly correlated with an antagonist pattern of muscle contraction. Enhanced long-latency reflexes were not found. Other characteristics of essential tremor were not significantly correlated. It is concluded that essential tremor can not be classified into subtypes.

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.