Lisa M. Shulman

Acupuncture in clinical neurology.

BACKGROUND–A majority of people in the United States use alternative or complementary therapy at some point in their lives, and acupuncture is among the most frequently used modalities. Many United States medical schools offer courses in alternative medicine, and a growing number of insurers offer coverage for alternative therapies. This paper critically reviews our current knowledge about the safety and efficacy of acupuncture for neurologic conditions. REVIEW SUMMARY–Acupuncture is a safe procedure when performed by trained professionals. Complications from acupuncture are rare and mainly related to negligence of sterile technique. Studies of the therapeutic value of acupuncture are fraught with challenging methodologic problems, including the choice of a placebo, a suitable control treatment, and the technique of stimulation applied. Clinical trials of the use of acupuncture for pain syndromes (headache, neck, and back pain), stroke rehabilitation, Parkinson’s disease, multiple sclerosis, and substance abuse are reviewed. CONCLUSIONS–Based on the current literature, no definitive recommendation can be made regarding the efficacy of acupuncture for common pain syndromes including headache, and neck and back pain. Better quality clinical trials fail to demonstrate efficacy for the use of acupuncture as part of a rehabilitation program following stroke or as a treatment for drug addiction. Acupuncture may have a role in the treatment of sleep disturbance associated with Parkinson’s disease but was not efficacious for the primary symptoms of either Parkinson’s disease or multiple sclerosis. In light of increasing public interest and use of alternative therapies, this review may be helpful in promoting more discussion between patients and physicians about the use of acupuncture.

Rasagiline improves quality of life in patients with early Parkinson's disease

The objective of this study was to determine the effects of rasagiline as monotherapy on quality of life (QOL) in patients with early Parkinsons disease (PD). Rasagiline, a potent, second‐generation, irreversible, selective monoamine oxidase B inhibitor improves PD symptoms in patients with early PD. Patients with early untreated PD were randomly assigned to once‐daily rasagiline 1 mg/day, rasagiline 2 mg/day, or placebo in a 6‐month, double‐blind trial (n = 404). At the end of 6 months, patients entered the preplanned, active‐treatment phase in which those receiving 1 mg/day and 2 mg/day of rasagiline continued on their previously assigned dosages and those receiving placebo switched to rasagiline 2 mg/day, while maintaining blinding to treatment assignments. QOL was measured with the Parkinsons Disease Quality of Life questionnaire (PDQUALIF) at 0, 14, 26, and 52 weeks after randomization. Analysis of the change in PDQUALIF scores from baseline to 6 months showed adjusted treatment effects (with 95% confidence interval) favoring rasagiline over placebo of −2.91 units (−5.19, −0.64, P = 0.01) for the 1 mg/day group and −2.74 units (−5.02, −0.45, P = 0.02) for the 2 mg/day. Subscore analysis attributed most of this benefit to the self‐image/sexuality domain. At 12 months (n = 266), with all groups receiving rasagiline for at least 6 months, no significant differences in PDQUALIF scores were seen between groups. Rasagiline improved QOL compared with placebo. This QOL improvement appears to be accounted for primarily by the symptomatic benefit of rasagiline.

The effect of pregnancy in Parkinson's disease

Pregnancy in patients with Parkinsons disease (PD) is a rare occurrence. Previous reports based on retrospective analysis suggest that pregnancy may have a deleterious effect on PD. We describe the effects of pregnancy on the symptomatology of a 33‐year‐old woman with PD using quantitative neurologic and quality‐of‐life scales prepartum, intrapartum, and postpartum. During her pregnancy, she was only treated with carbidopa/levodopa. The pregnancy resulted in a normal full‐term vaginal delivery of a healthy infant. Significant worsening of this patients motor symptoms occurred during pregnancy without return to baseline at 15 months postpartum. Pregnancy may exacerbate PD and may have a long‐term negative impact on the course of the illness. This report may assist physicians in the counseling of patients with young‐onset PD who wish to consider pregnancy.

The use of dopamine agonists in very elderly patients with Parkinson's disease

Controversy exists regarding the use of dopamine receptor agonists in elderly patients with Parkinsons disease because of concern about a high rate of intolerable side effects.

Risperidone in Gilles de la Tourette syndrome

Gilles de la Tourette syndrome (GTS) is an inherited movement disorder characterized by the waxing and waning of multiple motor and vocal tics, usually of childhood onset. Although there is no known pathologic lesion associated with GTS, altered dopaminergic mechanisms seem important in tic production because of the effect of haloperidol and pimozide in suppressing motor and vocal tics. These neuroleptics are both potent D, antagonists. Atypical neuroleptics (eg, clozapine, risperidone) are defined as drugs tha t are antipsychotic with few or no extrapyramidal side effects and that have expanded therapeutic potential, particularly in treating the negative symptoms of schizophrenia. Risperidone, a n atypical neuroleptic, is a benzisoxazole derivative that combines potent serotonin (5-HTz) and dopamine (Dz) antagonistic properties. It is also a noradrenergic antagonist and an antihistamine. Risperidone, unlike clozapine, does not have a significant risk of agranulocytopenia. We report a patient with GTS who was successfully treated with risperidone. Case report. A 45-year-old man experienced a 2-month exacerbation of motor and vocal tics during a stressful time at his place of employment. The motor tics included facial, upper extremity, and truncal movement. The vocal tics were characterized by grunting noises as well as coprolalia. The patient required a piece of candy in his mouth in order to prevent the use of “bad words.” On examination, he had widespread and frequent multifocal motor tics. Occasional vocalizations (grunting) were noted. He was started on risperidone 1 mg b.i.d. Within 2 weeks and despite no change in his workplace environment, the motor and vocal tics were remarkably diminished. Coprolalia ceased. He had occasional tics in the right perioral region and right periocular region. No vocalizations were noted. Occasional stereotypic hand movements involving the left upper extremity remained unchanged. The tic disorder had been present since age nine. The tics had been reported to wax and wane throughout his teenage years, and included motor involvement of his shoulders, eyes, mouth, face, and neck a t various times. Vocalizations were never prominent. Family history of tic disorders and obsessivecompulsive symptoms was denied. During the next 2 months, risperidone continued to control his motor and vocal tics despite a dosage reduction to 1% mg/d. The dosage reduction was necessitated by the induction of akathisia. The patient continues on risperidone. Discussion. van der Linden et a12 reported that risperidone decreased motor and vocal tics in five patients with GTS. None of these patients developed extrapyramidal side effects with a mean daily dose of 4.3 mg., This report, and the effect in our patient, suggest that risperidone may be useful in suppressing motor and vocal tics in this disorder. Risperidone-induced parkinsonism occurs less frequently than with haloperidol when risperidone is used t o t reat acute exacerbations or chronic sch iz~phrenia .~?~ Owens5 suggested that neuroleptics whose side effect profile includes less acute and subacute drug-induced extrapyramidal features are also less likely to induce tardive dyskinesia. Risperidone’s extrapyramidal side effect profile with acute and subacute use suggests that the frequency of tardive dyskinesia in patients exposed to long-term risperidone may be less. Since the use of typical neuroleptics to treat GTS is accompanied by the risk of tardive dyskinesia, risperidone may be a safer drug t o use in the long-term treatment of GTS. Our patient did experience akathisia, indicating that risperidone is not completely devoid of extrapyramidal side effects, There is little evidence to suggest a role for the serotonergic system in the motor symptoms of GTS. Attempts to use 5hydroxytryptophan, methysergide, and the selective serotonin reuptake inhibitor chlorimipramine have not been of value in suppressing tics.‘ The S-HT, antagonistic properties of risperidone are probably not responsible for its therapeutic benefit in GTS; the D, antagonist activity is most likely responsible for tic suppression. This further extends the circumstantial evidence that dopaminergic mechanisms play a role in tic production in GTS.

Pramipexole in levodopa-treated Parkinson disease patients of African, Asian, and Hispanic heritage

Background: Little is known regarding the effects of antiparkinsonian drugs in US racial or ethnic minorities. Objective: To evaluate the safety, tolerability, and efficacy of adjunctive pramipexole in Parkinson disease (PD) patients of African, Asian, or Hispanic heritage stably treated with levodopa. Design: Multicenter, parallel-group, double-blind, randomized, placebo-controlled trial. Setting: Seventeen Parkinson Study Group sites in the United States and Puerto Rico. Patients: One hundred forty-four PD patients of African, Asian, or Hispanic heritage enrolled from January 1997 to August 1998 and observed until October 1998. Intervention: Subjects received pramipexole or placebo (3:1 ratio), 0.375 mg/d to a maximum tolerated dose (≤4.5 mg/d) over a 6-week period, achieving optimum levels (0.375, 1.5, 3.0, or 4.5 mg/d) in the 4-week maintenance period. Main Outcome Measure: Change in the sum of the Unified Parkinsons Disease Rating Scale parts 2 (activities of daily living) and 3 (motor) from baseline to week 10. Results: Parkinsonism improved (mean [SD] reduction in Unified Parkinsons Disease Rating Scale activities of daily living + motor score at 10 weeks, 10.27 [11.96] pramipexole vs 6.54 [13.58] placebo, P = 0.012) and was similar in each group. Adverse events occurred in 85.3% on pramipexole and 68.6% on placebo. Hallucinations and insomnia were more common on pramipexole than placebo (18 vs 0, P = 0.023, and 15 vs 0, P = 0.045, respectively). Conclusions: Pramipexole is an effective adjunctive antiparkinsonian therapy in PD patients of African, Asian, and Hispanic heritage. Tolerability and safety overall were similar among the groups, but differences in profiles of adverse effects and tolerability were suggested.

HIV encephalitis presenting with severe generalized chorea

We report a case of rapidly progressive encephalopathy and generalized chorea due to HIV encephalitis.The patient was a 24-year-old man known to be HIV-seropositive for 4 years. The severity of the movement disorder resulted in rhabdomyolysis. Sepsis developed and he died after a 21-day hospitalization. Pathologic study revealed prominent neuronal loss and gliosis of subcortical regions. Acute encephalopathy with generalized chorea may be a rare consequence of HIV encephalitis. NEUROLOGY 1996;46: 1163-1165

Modafinil for the treatment of excessive daytime sleepiness in Parkinson's disease: a case report.

We report a 59 year old woman with levodopa responsive Parkinsons disease who developed excessive daytime sleepiness [Epworth Sleepiness Scale (ESS) score of 13]. Treatment with Modafinil 400mg daily within two weeks produced a subjective improvement in her daytime sleepiness (ESS score after treatment is 8) with no significant change in her PD motor symptomotology.

Acquired abducens-trigeminal synkinesis

Acquired synkinesis after trauma affecting the oculomotor nerve was first described by Gowers in 1879.1 Several nerve combinations have been described, including congenital trigemino-oculomotor and trigemino-abducens synkinesis.2-4 We describe a patient with an acquired synkinesis of painful involuntary jaw closure triggered by voluntary leftward gaze. Case report. A 40-year-old man presented with the complaint of frequent involuntary forceful left jaw closure with horizontal gaze to the left. A motor vehicle accident at age 18 had resulted in traumatic brain injury. After prolonged coma, his neurologic deficits included left hemiparesis, dysarthria, and left ophthalmoparesis. He gradually regained strength. Dysarthria and diplopia remained. He had several ophthalmologic procedures performed on the left eye. Botulinum toxin injections to the extraocular muscles improved fusion, but he continued to have residual diplopia. Involuntary jaw closure began 5 years after his injury but before his eye surgery. Horizontal gaze to the left triggered forceful closure of the left mandible and …

Reply from the Authors: Niemann-Pick; type C

Reply from the Authors: We appreciate the comments of Drs. Patterson and Pentchev who have made major contributions to our understanding of NPC. As 38% of patients with adult-onset NPC developed psychosis and 81% developed dementia, their comment regarding the potential hazard …