Hypomimia Research Articles

A Case Report of Methylphenidate-Induced Dyskinesia.

Sir: Movement disorders have long been associated with a wide variety of medications and illicit drugs. Dopaminergic agents are well-known precipitants of various dyskinesias, including chorea, choreoathetosis, dystonia, and ballism. For example, levodopa-induced dyskinesias are a relatively common side effect of the treatment of Parkinson's disease, with up to 45% of patients affected after 5 years of such treatment.1 Stimulants, such as methylphenidate, have also been associated with dyskinesias. Most case reports, however, implicate large dosages2 or chronic use of stimulant medications.3 Another recognized effect of methylphenidate is the development of motor tics in children.4 In contrast, the case presented here involves the acute development of choreoathetosis in an elderly patient after only 2 small doses of methylphenidate, with rapid resolution of the movement disorder following discontinuation of the offending agent. Case report. Mr. A is an 87-year-old man with a history of Parkinson's disease, hypothyroidism, and depression. He was admitted to the medical service for progressive weakness and inability to manage his activities of daily living. Mr. A had been diagnosed with Parkinson's disease over 10 years ago. Treatment consisted of 3 tablets of carbidopa/levodopa sustained release, 50 mg/200 mg 3 times per day. Historically, Mr. A's compliance had been suboptimal, but over the prior 6 months, in-home nursing had optimized compliance. The patient was euthyroid on treatment with levothyroxine, 125 mg/day. His depression had been treated successfully with sertraline, 50 mg/day, for approximately 3 years. Psychiatric consultation was requested to evaluate Mr. A for depression as an etiology for his observed “failure to thrive.” Psychiatric assessment revealed a thin, elderly appearing man lying comfortably in bed. A mild pill-rolling tremor and cogwheel rigidity were noted on physical examination. Mr. A denied a subjective feeling of depression and, despite obvious bradykinesia and masked facies, did not appear clinically depressed. However, he was quite cognitively impaired, scoring only 17/30 on the Folstein Mini-Mental State Examination.5 (Mr. A lost 6 points for time and place disorientation. Immediate recall was intact. Delayed recall was impaired, with loss of 2 points. Attention was impaired on serial 7s, resulting in the loss of 3 points. The last 2 points were lost due to inability to follow a simple 3-step command.) The admission laboratory tests included electrolytes, liver function, thyroid-stimulating hormone, and a complete blood count. The only abnormality found was a mild normocytic anemia, with a hemoglobin level of 11.4 g/dL. The consultation service assessed Mr. A's primary problem not as a depressive disorder, but rather as a dementing process coupled with advanced Parkinson's disease. A complete laboratory workup for reversible causes of dementia was negative, and a computed tomographic scan of the head revealed cerebral volume loss and areas of periventricular hypodensity. Mr. A was placed on treatment with methylphenidate, 2.5 mg twice per day, by the medical service to improve appetite and “mood.” After only 2 doses of methylphenidate, the patient was found to have significant choreoathetosis and a change in mental status consistent with a delirium. Methylphenidate was subsequently discontinued and quetiapine, 25 mg twice per day, was initiated. Carbidopa/levodopa administration was maintained, although the dosing schedule was adjusted to ensure 8 hours between each dose. Mr. A responded well to the discontinuation of the methylphenidate and the administration of small doses of quetiapine. He experienced a significant resolution of the dyskinesia and a clearing of the delirium. The patient was subsequently discharged to a rehabilitation facility. Methylphenidate, when given in therapeutic doses, has recently been shown to increase extracellular dopamine in the human brain.6 This capacity of methylphenidate to increase dopamine within the striatum is the proposed mechanism by which methylphenidate and other stimulants may induce movement disorders. Mr. A's case is complicated by the presence of Parkinson's disease and concurrent therapy with carbidopa/levodopa, an agent known to be associated with iatrogenic dyskinesia. However, the temporal relationship between the start of methylphenidate therapy and the onset of the movement disorder suggests that the stimulant is the etiologic agent behind the observed choreoathetosis. The damage to the basal ganglia inherent in Parkinson's disease may provide a predilection to the development of movement disorders with dopaminergic medications. The development of Mr. A's choreoathetosis early in the course of low-dose methylphenidate treatment may indicate the importance of a “primed” brain in the development of dyskinesia associated with various dopaminergic stimulant medications.

Current Perspectives on the Lee Silverman Voice Treatment (LSVT) for Individuals With Idiopathic Parkinson Disease

Successful treatment of speech disorders in individuals with progressive neuro logical diseases can be challenging. Hillman, Gress, Haugraf, Walsh, and Bunting (1990) stated that “voice treatment for disorders that are degenerative is controversial since there is no expectation for recovery of function or that any improvement secondary to speech language pathology intervention will be maintained in the long term” (p. 308). Individuals with idiopathic Parkinson disease (IPD) have been particularly resistant to speech treatment, with the conventional wisdom being summarized by the statement that changes observed in the treatment room disappear on the way to the parking lot (Allan, 1970; Aronson, 1985; Greene, 1980; Sarno, 1968; Weiner & Singer, 1989). The consensus that speech treatment has not been effective for individuals with IPD is, perhaps, the basis for the report that of the 75%–89% of these individuals with voice and speech disorders, only 3%–4% receive speech treatment (Hartelius & Svensson, 1994; Oxtoby, 1982). The reduced ability to communicate is considered to be one of the most difficult aspects of IPD by many patients and their families. Soft voice, monotone, breathy, hoarse voice quality, and imprecise articulation (Darley, Aronson, & Brown, 1969a, 1969b; Logemann, Fisher, Boshes, & Blonsky, 1978), together with lessened facial expression (masked facies), contribute to limitations in communication in the vast majority of individuals with IPD (Pitcairn, Clemie, Gray, & Pentland, 1990a, 1990b). Although medical treatments, including neuropharmacological as well as neurosurgical methods, may be effective in improving limb symptoms, their impact on speech production remains unclear (Baker, Ramig, Johnson, & Freed, 1997; Kompoliti, Wang, Goetz, Leurgans, & Raman, 2000; Larson, Ramig, & Scherer, 1994; Rigrodsky & Morrison, 1970; Solomon et al., 2000; Wang, Kompoliti, Jiang, & Goetz, 2000; Wolfe, Garvin, Bacon, & Waldrop, 1975). In addition, previous speech treatment for individuals with IPD, focusing on articulation and rate, has limited efficacy data and limited evidence of long-term success. Recently, there has been great progress in understanding the function of the basal ganglia; this has shed light on the neural bases of IPD (Albin, 1995; Brooks, 1995; Hayes, Davidson, Keele, & Rafal, 1998; Mink, 1996; Wichmann & DeLong, 1993, 1996). Although many studies have used these findings to understand limb function in individuals with IPD (Rand & Stelmach, 1999; Weiss, Stelmach, Chaiken, & Adler, 1999), their application to voice and speech disorders has been infrequent. At this time, the neural mechanisms underlying speech, voice, and swallowing disorders in IPD are not well understood. Over the past 10 years, our research team has focused on improving speech disorders in individuals with IPD by directing attention to phonation (voice) as a key treatment element. Although disordered voice has been observed in the majority of individuals with IPD (Logemann et al., 1978; Oxtoby, 1982; Streifler & Hofman, 1984), it has until recently been given limited attention in treatment and has been overlooked for its contribution to improving speech intelligibility. Treating voice in individuals with IPD has generated shortand long-term efficacy data for a speech treatment in this population (Ramig, Countryman, O’Brien, Hoehn, & Thompson, 1996; Ramig, Countryman, Thompson, & Horii, 1995; Ramig, Sapir, Countryman, Pawlas, O’Brien, Hoehn, & Thompson, 2001; Ramig, Sapir, Fox, & Countryman, 2001). This treatment— known as the Lee Silverman Voice Treatment (LSVT)—has as its essential concepts (a) exclusive focus on voice (specifically vocal

Complicated Delirium in a Cancer Patient Successfully Treated with Olanzapine

Delirium is common among cancer patients, especially those with advanced disease. Typical treatment involves addressing the underlying cause if possible; eliminating nonessential and/or other drugs that can worsen confusion, manipulating the environment; and administering antipsychotic drugs to control symptoms and agitated behavior, and attempt to clear the patient’s sensorium. The newer atypical antipsychotics may have potential in the treatment of delirium and also have the added benefit of causing less akithisia and other extrapyramidal side effects. This is illustrated by the case of a 59-year-old woman with leukemia and pain of unclear etiology who developed a delirium and a moderate to severe extrapyramidal syndrome (EPS) in the setting of escalation of her pain medications and concomitant escalation of prochlorperazine. The patient presented with confusion and moderate to severe cogwheeling rigidity, masked facies, bradykinesia, and tremor. Additionally, the patient had a relatively recent history of subdural hematoma and one seizure. Conservative management including eliminating multiple nonessential medications (including the prochlorperazine); changing her opioid analgesic; providing a 24-hour companion; and administering low doses of haloperidol (0.5 mg–2.0 mg) were not effective in treating the patient’s delirium. The patient’s EPS was dramatically worse following haloperidol doses. After approximately 1 week without improvement, the patient was started on olanzapine 5 mg daily with initial improvement but with residual confusion in the evenings and overnight. The dose was titrated up to 10 mg nightly with 2.5 mg as needed during the day. After 3 days on this regimen, the patient’s mental status exam was normal and she was discharged home. We discuss the potential utility of this atypical antipsychotic in the palliative care setting.

Generalized eruptive keratoacanthoma of Grzybowski

A patient with generalized eruptive keratoacanthoma of Grzybowski is described. Our findings, along with those of the 21 reported cases from the world literature, are summarized. This rare variant of keratoacanthoma most commonly affects patients in the fifth to seventh decades of life and appears as a generalized eruption of hundreds to thousands of follicular papules. These small papules often have a keratotic center and demonstrate the microscopic features of keratoacanthoma. Marked facial involvement is characteristic and can lead to masked facies with ectropion. Severe pruritus, mucosal lesions, and koebnerization are features of the disease. The course is chronic and the response to therapy is poor, although a few patients have improved with the use of systemic retinoids.

Three-year follow-up of older schizophrenics: Extrapyramidal syndromes, psychiatric symptoms, and ventricular brain ratio

Longitudinal evaluation of psychiatric patients often yields information that cross-sectional study does not. We previously examined 31 older (age > 55) chronic schizophrenics for prevalence of extrapyramidal side effects, severity of psychiatric symptoms, and ventricular brain ratio (VBR). We reexamined 22 of these patients after 2–4 years. Tardive dyskinesia (TD) and drug-induced parkinsonism (DIP) were common (mean prevalences were 52% and 62%, respectively) and often occurred together (38%). The overall prevalences of the disorders did not change significantly with time, although there was some individual fluctuation in diagnosis. Severity of TD was constant, but severity of DIP decreased, probably because neuroleptic doses were significantly decreased. Magnitude of DIP was positively correlated with VBR and severity of negative symptoms of schizophrenia. The correlation of DIP and negative symptoms occurred primarily because of the similarity between masked facies and blunted affect. VBR did not change over the follow-up period. Negative symptoms of schizophrenia were prevalent, moderately severe, and quite stable over time in this cohort. Positive symptoms were less severe but highly variable between examinations.

The Lewy body variant of Alzheimer's disease

Thirty-six clinically diagnosed and pathologically confirmed Alzheimer's disease (AD) patients included 13 with cortical and subcortical Lewy bodies (LBs). The patients with LBs appeared to constitute a distinct neuropathologic and clinical subset of AD, the Lewy body variant (LBV). The LBV group showed gross pallor of the substantia nigra, greater neuron loss in the locus ceruleus, substantia nigra, and substantia innominata, lower neocortical ChAT levels, and fewer midfrontal tangles than did the pure AD group, along with a high incidence of medial temporal lobe spongiform vacuolization. Analysis of neuropsychological tests from 9 LBV subjects and 9 AD patients matched for age and degree of dementia revealed greater deficits in attention, fluency, and visuospatial processing in the LBV group. Similar comparisons of neurologic examinations showed a significant increase in masked facies; in addition there was an increase in essential tremor, bradykinesia, mild neck rigidity, and slowing of rapid alternating movements in the LBV group. Extremity rigidity, flexed posture, resting tremor, or other classic parkinsonian features were not characteristic of the LBV patient. In some cases, it may be possible to diagnose LBV premortem on the basis of the clinical and neuropsychological features.

Chronic manganese intoxication.

Six men developed chronic manganese intoxication while employed in a manganese ore crushing plant. Symptoms included somnolence, gait imbalance, slurred speech, and impaired fine movements. Signs included bradykinesia, postural instability, impaired arising ability, masked facies, and speech disorder. One patient was exceptional in that his major symptoms did not develop until three years after leaving exposure. Levodopa, up to 8 gm/day, was ineffective in three patients. Our cases and those in the literature indicate that, in the absence of rigidity or dystonia or both, levodopa is ineffective in chronic manganese intoxication. Intravenous edetic acid (EDTA) infusions were followed by temporary improvement in four individuals. Increased urinary excretion of manganese during edetic acid infusion was observed in our cases and in two controls and thus does not appear to assist in diagnosing chronic manganese intoxication.

The effect of thalamotomy on the progress of unilateral Parkinson's disease.

LTHOUGH tremor and rigidity are frequently unilateral at the onset of Parkinson's disease, these signs usually spread to the opposite side of the body. Certain patients with unilateral tremor and rigidity, however, appear to be cured by successful thalamotomy. Cooper 1 has proposed alternative hypotheses to explain the effect of thalamic surgery in these patients: 1) a thalamotomy that permanently abolishes unilateral tremor and rigidity prevents spread to the opposite side of the body by interrupting the pathways in the basal ganglia subserving the propagation of the disease process; or 2) thalamotomy has no effect on the progress of tremor and rigidity to the opposite side of the body, and those patients with unilateral tremor and rigidity who appear to be cured by successful surgery have a benign form of Parkinson's disease. To study these hypotheses, we examined 72 patients approximately 5 years after they had undergone cryosurgical ventrolateral thalamotomy for tremor and rigidity which, at the time of surgery, were confined to one side of the body. Material and Methods For the purposes of this study, unilateral Parkinson's disease was defined as tremor and rigidity confined to the extremities of one side of the body. Masked facies, balance disturbances, akinesia, and other vegetative signs of Parkinson's disease were not included in this definition. From the St. Barnabas Hospital neurosurgical files subsequent to January 1, 1963, we selected the first 100 patients whose tremor and rigidity were unilateral at the time of surgery. Each patient was then contacted to arrange an interview

Generalized Eruptive Keratoacanthoma

Three cases of generalized eruptive keratoacanthoma are reported, and the findings in these and in four cases from the literature are summarized. The seven cases represented both men and women, and ages ranged from 32 to 57 years. A discrete small papule of keratoacanthoma is the primary lesion, and larger lesions often occur. Lesions may be follicular and so closely set as to simulate keratoderma. Linear groups of lesions, masked facies with ectropion, mucosal lesions, and severe pruritus are special features. Histologically, all lesions, including those of mucous membranes, are keratoacanthomas. In this series, no associated diseases were noted. Methotrexate did not help two patients in whom it was tried, but local applications of vitamin A provided objective and subjective relief.

USE OF CURARE IN OIL IN TREATMENT OF SPASTICITY FOLLOWING INJURY OF THE SPINAL CORD

WEST,1Burman,2Bennett3and others described the use of preparations of curare in treatment of various syndromes exhibiting spasticity, tremor and rigidity. They found that curare diminished hypertonia, tremor and involuntary movements. The clinical effect, however, was usually transient and therefore of questionable therapeutic value. Denhoff and Bradley,4in a group of spastic children, found that the initial period of response to effective doses was characterized by masked facies, head drop and mental confusion. After these unpleasant reactions had worn off, the useful clinical effect became evident. These therapeutic experiments were carried out with aqueous solutions of the drug, used either intravenously or intramuscularly. In the present study a group of patients showing intense spasticity accompanying injury to the spinal cord were treated with aqueous solutions of curare. Eleven patients with extreme spasticity were chosen from a large group. Of these 11, 9 had complete paraplegia