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Jonathan W Mink

Publications and source records attributed to Jonathan W Mink.

At least 19 recordsLinked to original sources
PubMed2006

Recent advances in Tourette syndrome research.

Tourette syndrome (TS) is a developmentally regulated neurobehavioral disorder characterized by involuntary, stereotyped, repetitive movements. Recent anatomical and neuroimaging studies have provided evidence for abnormal basal ganglia and dopaminergic function in TS. Basic research on striatal inhibitory mechanisms and dopaminergic function complements the recent neuroimaging and anatomical data. Parallel studies of basal ganglia participation in the normal performance and learning of stereotyped repetitive behaviors or habits has provided additional insight. These lines of research have provided new pieces to the TS puzzle, and their increasing convergence is showing how those pieces can be put together.

Basal Ganglia↗
PubMed2006

Relative risk of spread of symptoms among the focal onset primary dystonias.

Adult-onset primary torsion dystonia (PTD) may spread to multiple body parts, but the relative risk of spread by site of onset of dystonia has not been well characterized. We retrospectively identified 602 patients with PTD out of 1,500 dystonia patients in our electronic database and extracted age at onset, site of onset, family history, and spread. Survival analyses were performed for groups based on site of onset, and hazard ratios compared relative risk of spread across groups. Patients with adult-onset blepharospasm were more likely to spread (31% past the head) than those with dystonia starting in the neck (9%), larynx (12%), or upper extremities (16%). Hazard ratios proved that the blepharospasm group had the greatest relative risk of spread. The rate of spread after onset varied significantly between the different groups. Most spread occurred in the first 1 to 2 years after onset of blepharospasm, whereas the risk of spread was relatively constant over time in cervical and laryngeal dystonia. Different sites of onset of PTD confer different risks of spread, important for clinical prognosis. Different risks of spread may provide clues about underlying pathogenesis of adult-onset primary dystonias.

Adult↗
PubMed2006

Postural tremor suppression is dependent on thalamic stimulation frequency.

Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) reduces tremor in people with essential tremor (ET), yet the dependence of tremor suppression on stimulation frequency remains unclear. To address this issue, we tested tremor suppression for three 15-second measurements during a variety of stimulation frequencies in 11 ET patients treated with VIM DBS. Stimulation frequencies at or above 100 Hz produced maximal benefit; higher frequencies provided no additional benefit. If this short-term measure predicts long-term response in routine activities at home, then this stimulation frequency setting will prolong battery half-life compared to higher frequency settings. These findings suggest that ET patients treated with VIM DBS may receive adequate benefit from stimulation frequencies about 100 Hz and this setting compared to commonly used higher settings will prolong battery life of surgically implanted pulse generators.

Aged↗
PubMed2006

Patient selection and assessment recommendations for deep brain stimulation in Tourette syndrome.

In response to recent publicity regarding the potential use of deep brain stimulation (DBS) for reducing tic severity in Tourette's syndrome (TS), the Tourette Syndrome Association convened a group of TS and DBS experts to develop recommendations to guide the early use and potential clinical trials of DBS for TS and other tic disorders. The goals of these recommendations are to ensure that all surgical candidates are (1) fully informed about the risks, benefits, and alternative treatments available; (2) receive a comprehensive evaluation before surgery to ensure that DBS is clearly the appropriate clinical treatment choice; and (3) that early clinical experience will be documented publicly to facilitate rational decision-making for both clinical care and future clinical trials.

Deep Brain Stimulation↗
PubMed2006

New treatments for tic disorders.

Tics vary in severity from infrequent and barely noticeable to nearly continuous and highly disruptive. Treatment of tic disorders depends on the severity of the tics, the distress they cause, and the effects they have on school, work, or daily activities. Many tics do not interfere with school or everyday life and do not require specific treatment. Comorbid disorders such as attention deficit hyperactivity disorder, anxiety, and obsessive-compulsive disorder occur in more than 50% of patients. The associated comorbidity can be more bothersome than the tics themselves. Treatment should be aimed at the most troubling symptom. Education and reassurance are often sufficient for mild and occasional tics. For tics of moderate severity, clonidine and guanfacine have a reasonable safety profile. They are considered as first-line medications. With clonidine, start with 0.05 mg at bedtime. Increase as needed and as tolerated by 0.05 mg every 4 to 7 days to a maximum dosage of 0.3 to 0.4 mg/day divided three or four times a day. With guanfacine, start with 0.5 mg at bedtime. The dosage may be increased as needed and as tolerated by 0.5 mg every week to a maximum dosage of 3 to 4 mg/day, divided twice a day. There are emerging data that behavioral therapy is effective for treatment of tics in some individuals. Dopamine receptor blockers are the most potent medications for treating severe tics. The efficacy appears to be proportionate to the affinity for dopamine D2 receptors. Thus, standard antipsychotic medications such as haloperidol, pimozide, or fluphenazine are the most potent. However, these medications commonly cause bothersome side effects. Therefore, we recommend use of atypical neuroleptics before standard neuroleptics in most patients. Risperidone is usually the first choice and may have efficacy for behavior problems that often accompany tics. Start with 0.01 mg/kg/dose once a day; dosage may be increased by 0.02 mg/kg/day at weekly intervals, up to 0.06 mg/kg/dose once a day. Ziprasidone and olanzapine are reasonable alternatives.

Journal Article↗
PubMed2006

Standardized assessment of behavior and adaptive living skills in juvenile neuronal ceroid lipofuscinosis.

We obtained information about the behavioral, psychiatric, and functional status of 26 children (13 males, 13 females) with juvenile neuronal ceroid lipofuscinosis (JNCL; mean age 12y 3mo [SD 3y 4mo]; range 6y 9mo to 18y 8mo). Twenty-five children had visual impairment and 18 were known to have a positive seizure history before enrollment. Parents completed the Child Behavior Checklist, Scales of Independent Behavior - Revised, and a structured interview to assess obsessive-compulsive symptoms. Participants exhibited a broad range of behavioral and psychiatric problems, rated as occurring frequently and/or as severe in more than half of the sample. Males and females did not differ with regard to the number of behavioral and psychiatric problems. Children were also limited in their ability to perform activities of daily living, including self-care, hygiene, socialization, and other age-appropriate tasks. Results provide a quantitative baseline for behavioral and psychiatric problems and functional level in JNCL, against which further decline can be measured. Longitudinal assessment of behavioral and psychiatric symptoms and functional abilities is continuing and will provide much-needed data on the natural history of JNCL.

Activities of Daily Living↗
PubMed2006

Deep brain stimulation.

Deep brain stimulation (DBS) has provided remarkable benefits for people with a variety of neurologic conditions. Stimulation of the ventral intermediate nucleus of the thalamus can dramatically relieve tremor associated with essential tremor or Parkinson disease (PD). Similarly, stimulation of the subthalamic nucleus or the internal segment of the globus pallidus can substantially reduce bradykinesia, rigidity, tremor, and gait difficulties in people with PD. Multiple groups are attempting to extend this mode of treatment to other conditions. Yet, the precise mechanism of action of DBS remains uncertain. Such studies have importance that extends beyond clinical therapeutics. Investigations of the mechanisms of action of DBS have the potential to clarify fundamental issues such as the functional anatomy of selected brain circuits and the relationship between activity in those circuits and behavior. Although we review relevant clinical issues, we emphasize the importance of current and future investigations on these topics.

Animals↗
PubMed2006

Definition and classification of negative motor signs in childhood.

In this report we describe the outcome of a consensus meeting that occurred at the National Institutes of Health in Bethesda, Maryland, March 12 through 14, 2005. The meeting brought together 39 specialists from multiple clinical and research disciplines including developmental pediatrics, neurology, neurosurgery, orthopedic surgery, physical therapy, occupational therapy, physical medicine and rehabilitation, neurophysiology, muscle physiology, motor control, and biomechanics. The purpose of the meeting was to establish terminology and definitions for 4 aspects of motor disorders that occur in children: weakness, reduced selective motor control, ataxia, and deficits of praxis. The purpose of the definitions is to assist communication between clinicians, select homogeneous groups of children for clinical research trials, facilitate the development of rating scales to assess improvement or deterioration with time, and eventually to better match individual children with specific therapies. "Weakness" is defined as the inability to generate normal voluntary force in a muscle or normal voluntary torque about a joint. "Reduced selective motor control" is defined as the impaired ability to isolate the activation of muscles in a selected pattern in response to demands of a voluntary posture or movement. "Ataxia" is defined as an inability to generate a normal or expected voluntary movement trajectory that cannot be attributed to weakness or involuntary muscle activity about the affected joints. "Apraxia" is defined as an impairment in the ability to accomplish previously learned and performed complex motor actions that is not explained by ataxia, reduced selective motor control, weakness, or involuntary motor activity. "Developmental dyspraxia" is defined as a failure to have ever acquired the ability to perform age-appropriate complex motor actions that is not explained by the presence of inadequate demonstration or practice, ataxia, reduced selective motor control, weakness, or involuntary motor activity.

Apraxias↗
PubMed2006

Neurobiology of basal ganglia and Tourette syndrome: basal ganglia circuits and thalamocortical outputs.

In summary, the scheme of basal ganglia function presented here, in conjunction with known features of anatomical organization and dopamine neurotransmission provides a hypothesis for the pathophysiology of tics. According to the hypothesis, clusters of striatal neurons (matrisomes) become abnormally active in inappropriate contexts leading to inhibition of GPi or SNpr neurons that would normally be active to supress unwanted movements. The inhibition of htese GPi or SNpr neurons would then disinhibit thalamocortical circuits. Leading to the production of tics. Activity-dependent dopamine effects would inappropriately reinforce these activity patterns leading to stereotyped repetion. Over time, exactly which striatal neuronal clusters are overactive may change under various influences so that the produced movement change over time. This hypothesis is testable directly but requires a valid animal model of tics or higher resolution functional imaging techniques. Continuing work on basic basal ganglia physiology, pathophysiology, and functional imaging in TS is advancing our knowledge of neural circuit abnormalities in TS, but much more work is still needed.

Animals↗
PubMed2005

Novel CLN3 mutation predicted to cause complete loss of protein function does not modify the classical JNCL phenotype.

Juvenile Neuronal Ceroid Lipofuscinosis (JNCL), or Batten disease, is a childhood neurodegenerative disease that is characterized clinically by progressive visual loss, seizures, dementia, and motor incoordination. Children affected with this disease tend to develop normally for the first 5 years of life. However, once disease onset occurs, they decline rapidly and die in their late 20s to early 30s. Though this represents the typical disease course, the onset and severity of disease symptoms can vary. This variability is presumed to be the result of both differences in the causative genetic mutation in the CLN3 gene as well as environmental influences. Most cases of JNCL are caused by a 1 kb deletion in the CLN3 gene, resulting in a frameshift mutation predicted to leave the first 153 amino acids of the CLN3 protein intact, followed by the addition of 28 novel amino acids. Here we report the discovery of a novel mutation identified as a G to T transversion at nucleotide 49 (G49T) in exon 2 of CLN3, introducing a premature stop codon (E17X) near the N-terminus. This mutation represents the most 5' mutation described to date. The patient examined in this study was heterozygous for the common 1 kb deletion and E17X. She had classical disease progression, suggesting that this mutation in CLN3 mimics the more prevalent 1 kb deletion and that progression of JNCL is predominantly the result of loss of CLN3 function.

Adult↗
PubMed2005

Microinfusion of antineuronal antibodies into rodent striatum: failure to differentiate between elevated and low titers.

An autoimmune-mediated mechanism has been proposed for several pediatric movement disorders. In a three-center (Brown, Yale, and Johns Hopkins) collaborative effort, serum antineuronal antibodies (ANAb) were measured by use of ELISA or immunohistochemical techniques on 35 children (mean age 11.4 years) with Tourette syndrome, attention deficit hyperactivity disorder, and/or obsessive compulsive disorder. Eight sera, 4 containing the highest and 4 the lowest levels of ANAb, were identified at each institution. Selected sera (total of 9 with elevated and 7 with low ANAb) were re-encoded and sent to each center for infusion into the ventrolateral striatum of 16 male Sprague-Dawley rats. Animals were observed for behavioral abnormalities for 3 days before the start of infusion, during infusion on days 2-4, and for 2 days after infusion. Combined stereotypy scores increased after antibody infusion, but there was no significant effect based on serum titer (p=0.85). Scores differed among centers, but analyses based on individual institutional data again failed to show an effect based on elevated or low ANAb values (Brown, p=0.95; Yale and Johns Hopkins, p=0.81). Post hoc studies with sham surgery and infusion of phosphate-buffered saline support suggestions of nonspecific behavioral effects unrelated to antibody titer. This report emphasizes that any conclusions about antibody-mediated movement disorders that are based upon results from the rodent infusion model must be considered with caution.

Adolescent↗
PubMed2005

Masturbation in infancy and early childhood presenting as a movement disorder: 12 cases and a review of the literature.

PURPOSE: Infantile masturbation (gratification behavior) is not commonly identified as a cause of recurrent paroxysmal movements. Extensive and fruitless investigations may be pursued before establishing this diagnosis. Sparse literature is available regarding masturbatory behavior as a whole, but literature available as case reports describes common features. The purpose of this case series is to describe consistent features in young children with posturing accompanying masturbation. METHODS: Twelve patients presenting to a pediatric movement disorders clinic with a suspected movement disorder were determined to have postures and movements associated with masturbation. We reviewed the clinical history, examination, and home videotapes of these patients. RESULTS: Our patients had several features in common: (1) onset after the age of 3 months and before 3 years; (2) stereotyped episodes of variable duration; (3) vocalizations with quiet grunting; (4) facial flushing with diaphoresis; (5) pressure on the perineum with characteristic posturing of the lower extremities; (6) no alteration of consciousness; (7) cessation with distraction; (8) normal examination; and (9) normal laboratory studies. CONCLUSIONS: The identification of these common features by primary care providers should assist in making this diagnosis and eliminate the need for extensive, unnecessary testing. Direct observation of the events is crucial, and the video camera is a useful tool that may help in the identification of masturbatory behavior.

Child, Preschool↗
PubMed2004

Effect of stimulation frequency on tremor suppression in essential tremor.

We sought to determine the effect of deep brain stimulation (DBS) frequency on tremor suppression in essential tremor (ET) patients with deep brain stimulators implanted in the ventral intermediate nucleus (VIM) of the thalamus. A uniaxial accelerometer was used to measure tremor in the right upper extremity of subjects with a diagnosis of ET who had DBS electrodes implanted in the left VIM. The root-mean-square acceleration was used as the index of tremor magnitude and normalized to the OFF DBS condition. There was a highly significant inverse sigmoidal relationship between stimulation frequency and normalized tremor acceleration (X(2)/DoF = 0.42, r(2) = 0.997). Tremor acceleration had a nearly linear response to stimulation frequencies between 45 and 100 Hz with little additional benefit above 100 Hz. These findings have two important implications. Clinically, frequency of thalamic stimulation is an important variable for optimal tremor control with maximal benefit achieved with 100 to 130 Hz in most patients. Second, thalamic DBS provides tremor benefit in a graded manner and is not an all-or-nothing phenomenon.

Adult↗
PubMed2004

Psychogenic movement disorders in children.

A common problem in neurology is the existence of disorders that present with neurologic symptoms but do not have an identifiable neurologic basis. These disorders are often thought to have a psychologic basis. Abnormal movements are among the most frequent symptoms in psychogenic neurologic disorders. Although these disorders have not been studied extensively in children, clinical experience in our busy pediatric movement disorders clinic and many case reports support their existence in this age group. Elements of history, physical examination, and therapeutic intervention must be combined to construct a clear diagnosis of a psychogenic movement disorder. This article reviews the diagnosis and treatment of these disorders and includes two illustrative cases. Review of the current literature reveals a need for prospective trials to provide a solid foundation for better diagnosis and treatment of these disorders.

Adolescent↗