Juvenile Parkinsonism: a heterogeneous entity

We studied the clinical features, laboratory investigation, management and natural history of a cohort of patients with Juvenile Parkinsonism (JP), seen at a tertiary referral centre. JP was defined as Parkinsonism with onset at age 20 years or less. Six patients (five male, one female) entered the study. The mean age at onset of Parkinsonism was 12.5 years (range 7-19) and the mean follow-up time was 49.3 months (range 40-57). Bradykinesia, rigidity, and postural instability were observed in all patients and five subjects had tremor. Dystonia was present in four subjects. Other clinical features were dementia (five subjects), supranuclear ophthalmoparesis (five subjects), seizures (three subjects), multifocal myoclonus (one subject), decreased deep reflexes (one subject), pyramidal signs (one subject). Family history of Parkinson's disease (PD) was positive in one subject. Work-up for Wilson's disease was negative in all patients. Neuroimaging studies showed cortical atrophy in two subjects and mild brainstem atrophy in two others. Sea-blue histiocytes were found in one subject. L-dopa improved the Parkinsonism in all subjects but four rapidly developed fluctuations and dyskinesias, requiring, in one, stereotaxic surgery. After a mean disease duration of 6.5 years, five subjects require assistance for performance of all daily activities. JP is a heterogeneous clinical entity. In the majority of patients, no underlying cause is identified. The unusual clinical features suggest most subjects have a CNS degenerative disease distinct from PD. There is, however, evidence suggesting that PD may rarely cause JP. Gangliosidosis is another cause of L-dopa-responsive JP. Regardless of the cause, in the present study JP displays an aggressive and rapidly progressive course in most patients.     

Juvenile Parkinsonism with Marked Diurnal Fluctuation

Abstract: We presented a report on four cases of juvenile parkinsonism with a marked diurnal fluctuation of symptoms and dystonia. Among parkinsonian signs, rigidity fluctuated the most and increasing rigidity by passive or active movements or emotional stress was observed. When we analyzed patients previously reported, in addition to bur own new patients, apart fnom the diurnal fluctuation and predominant occurrence in females, many similarities to Yokochi's third group of juvenile parkinsonism were found. In the previous reports, the patients with the marked fluctuation, of parkinsonian symptoms have not always shown dystonia. The changes of symptoms in relation to menstruation and pregnancy were other characteristic features in our three female patients. Here we proposed that for the present, it is preferable to call this disorder "juvenile parkinsonism with a marked diurnal fluctuation."     

Exercise alleviates Parkinsonism: clinical and laboratory evidence

The present review examines the putative benefits for individuals afflicted with Parkinsonism, whether in the clinical setting or in the animal laboratory, accruing from different exercise regimes. The tendency for patients with Parkinson's disease (PD) to express either normal or reduced exercise capacity appears regulated by factors such as fatigue, quality-of-life and disorder severity. The associations between physical exercise and risk for PD, the effects of exercise on idiopathic Parkinsonism and quality-of-life, the effects of exercise on animal laboratory models of Parkinsonism and dopamine (DA) loss following neurotoxic insults, and the effects of exercise on the DA precursor, L-Dopa, efficacy are examined. It would appear to be case that in view of the particular responsiveness of the dopaminergic neurons to exercise, the principle of 'use it or lose' may be of special applicability among PD patients.     

Clinical and Neuropathological Study of a Familial Case of Juvenile Parkinsonism

Abstract: This is a detailed autopsy case of rare juvenile parkinsonism with dominant heredity. The patient displayed parkinsonian symptoms which began at the age of 24, and expired in a state of quadriplegia-in-flexion at 35. In the later stage, myoclonic jerks, epileptiform convulsions and dementia appeared. L-dopa was effective only in the early stages. The autopsy revealed severe degeneration and the formation of atypical Lewy bodies in the cerebral cortex, as well as typical lesions of idiopathic parkinsonism with a Lewy body formation in the brain stem. This case was considered to belong essentially to idiopathic parkinsonism. The pathology of juvenile parkinsonism is reviewed briefly.     

Juvenile bipolar disorder in Brazil: clinical and treatment findings.

BACKGROUND: Because few studies were conducted to evaluate bipolar disorder in children and adolescents outside North America, this investigation aims to describe clinical features, pattern of comorbidities, and response to pharmacologic treatment in a sample of youths with bipolar disorder (BD) from a pediatric psychopharmacology outpatient clinic in Brazil. METHODS: We performed a retrospective chart review of all patients under age 15 with BD diagnoses who were evaluated and treated in our clinic from 1998-2001. A comparison sample of subjects with attention-deficit/hyperactivity disorder (ADHD) without BD (n = 362) was also evaluated. RESULTS: The prevalence of juvenile BD in our sample was 7.2% (36/500) (95% confidence interval = 5.2-9.9). Irritable mood was detected in 91.7% of the bipolar patients. The main comorbidity found was ADHD (58.3%). Children with BD had significantly higher rates of abnormally elevated CBCL scores in the externalizing dimension, anxiety and depression, delinquent behavior, and aggressive behavior scales than ADHD subjects (p <.05). Most BD patients (78%) needed combination drug therapy to achieve symptomatic control. CONCLUSIONS: Our results replicate clinical and treatment findings from U.S. investigations in a different culture demonstrating that juvenile BD is not a rare disorder in clinical samples.     

Juvenile parkinsonism: ventricular CSF biopterin levels and clinical features.

Total biopterin (T-BP) levels in the ventricular cerebrospinal fluid (CSF) and clinical features of 19 patients with juvenile parkinsonism (JP: Parkinson's disease manifesting below the age of 40) were evaluated and compared with 61 patients with classical Parkinson's disease (classical PD: symptoms developing at the age of 40 or above). The JP patients were divided into two subgroups: JP-I; those with good response to levodopa followed by marked motor fluctuations and dopa-induced dyskinesias (DID), JP-II; those with milder response than JP-I with less fluctuations and DID being more similar to classical PD. Both of the mean ventricular CSF T-BP concentrations in the JP and classical PD patients were significantly lower than that in neurological controls. Moreover, the mean T-BP level in the JP-I was markedly lower than that in the JP-II or classical PD. Total biopterin levels revealed a gaussian distribution in the classical PD. However, a bimodal distribution was noted in the JP, with the lower peak consisting of only JP-I patients. These results seem to indicate that JP-II represents early-onset classical PD, while JP-I represents a distinct subgroup having a different physiopathology from classical PD.     

Juvenile myoclonic epilepsy: a clinical and sleep EEG study.

Juvenile myoclonic epilepsy (JME) is characterized by myoclonic jerks on awakening, generalized tonic--clonic seizures (GTCS) and is associated with absence seizures in more than one third of cases. Fifteen patients with juvenile myoclonic epilepsy were studied with regard to their clinical profile, EEG data and sleep EEG findings. There was a delay in the diagnosis of JME (mean of 3.5 years) due to various reasons. Sleep deprivation was the most common precipitating factor for triggering seizures, followed by fatigue. Routine EEGs were abnormal in 73.33% of cases only and had misleading findings in 6.66%. Sleep EEGs were abnormal in 100% of cases with generalized spikes, polyspikes and slow wave discharges. Discharge rates on sleep EEGs typically increased significantly during the transition phase (i.e. the asleep to awakening stage) and we consider this to be a specific finding in appropriate clinical setting. Sleep EEGs are a more sensitive and specific tool for the diagnosis of JME while routine awake EEGs may miss or mislead.     

Juvenile levodopa‐responsive Parkinsonism with early orobuccolingual dyskinesias and cognitive impairment

A 13‐year old girl presented with slowly progressive rest tremor of the hands, bradykinesia, and rigidity. The symptoms improved with dopaminergic medications, but severe drug‐induced dyskinesias developed early. She subsequently developed cognitive slowing and difficulty initiating saccadic eye movements. She went on to have deep brain stimulation surgery. Experts discuss the syndromal diagnosis and predict the underlying pathology. The pathological diagnosis is given and clinical learning points are considered. © 2010 Movement Disorder Society     

Juvenile neuroaxonal dystrophy: clinical, electrophysiological, and neuropathological features.

We describe 2 brothers with progressive myoclonus epilepsy that began in the second decade and was associated with cerebellar ataxia and intellectual deterioration. Electroencephalographic and cerebral evoked potential studies showed findings associated with myoclonus epilepsy. Neuropathological examination of 1 of the brothers, who died at age 23 years, revealed widespread changes of neuroaxonal dystrophy without pigment deposition in the basal ganglia. We propose the term juvenile neuroaxonal dystrophy (JNAD) to distinguish this condition on clinical grounds from infantile neuroaxonal dystrophy on the one hand, and on clinical and pathological grounds from Hallervorden-Spatz disease on the other hand. JNAD, while exceedinly rare, must be considered in the differential diagnosis of the progressive myoclonus epilepsies.     

Juvenile Huntington chorea: clinical, ultrastructural, and biochemical studies.

A brain biopsy from a 20-year-old patient whose clinical course was marked by progressive dementia and chorea since age 10 years showed increased amounts of lipofuscin, abnormal mitochondria, and other organelles in cortical neurons, neurites, and astrocytes. Juvenile Huntington chorea was confirmed at autopsy. High levels of three histone-like proteins (molecular weight 10,000 to 16,000) in the microsomal fraction of purified neurons were found by SDS-polyacrylamide gel electrophoresis. Fatty acids were abnormal in white matter sphingomyelin. These ultrastructural and biochemical findings conformed to those established in adult Huntington chorea, thus strengthening the concept of a uniform pathologic process in adult and juvenile Huntington diseases in spite of some clinical and histologic differences.     

Juvenile myoclonic epilepsy: clinical and EEG features

We aimed to characterize the clinical profile and EEG features of 43 patients with juvenile myoclonic epilepsy. In a retrospective design we studied the records of, and re-interviewed, 43 patients diagnosed with JME from the epilepsy clinic data base. Furthermore, available EEGs were re-evaluated. Of the patients 72% were female and 28% male. Average age of onset was 13 (5.5–22) years for absences, 16 (5.2–25) years for myoclonic seizures, and 16 (8–29) years for generalized tonic–clonic seizures. Forty-two percent reported asymmetric or unilateral myoclonic jerks. Commonly reported precipitating factors were sleep deprivation (84%), stress (70%), and alcohol consumption (51%). EEG findings included rapid spike-wave and polyspike-wave.     

Central pain: clinical and physiological characteristics.

OBJECTIVES--To study the clinical and pathophysiological features of central pain due to damage to the CNS. METHODS--156 patients (mostly with ischaemic strokes, some with infarct after subarachnoid haemorrhage and other cerebral conditions; one with bulbar and others with spinal pathology) with central pain have been investigated clinically and varying numbers instrumentally with respect to quantitative somatosensory perception thresholds and autonomic function. RESULTS--Pain onset was immediate in a minority; and from a week or two up to six years in > 60%. For those with supraspinal ischaemic lesions, the median age of onset was 59; dominant and non-dominant sides were equally affected. Two thirds of the patients had allodynia, including a previously undescribed movement allodynia apparently triggered from group I afferents. Most patients exhibited autonomic instability in that their pain was increased by physical and emotional stress and alleviated by relaxation; cutaneous blood flow and sweating may also be affected. Pain occurred within a larger area of differential sensory deficit. The critical deficit seems to be for thermal and pinprick sensations, which were more pronounced in areas of greatest than in areas of least pain; whereas low threshold mechanoceptive functions, if affected, did not vary between areas of greatest and least pain. Skinfold pinch (tissue damage) pain thresholds were only slightly affected in supraspinal cases, but greatly increased in patients with spinal lesions; thermal (heat) pain did not show this dissociation. CONCLUSION--The pathogenetic hypothesis which seems best to fit the findings is that there is up regulation or down regulation of receptors for transmitters, possibly mainly noradrenergic, over time.     

Juvenile myoclonic epilepsy of Janz: clinical observations in 60 patients.

We studied 60 patients with juvenile myoclonic epilepsy (JME). There was a high positive family history for epilepsy (33.3%). Age at onset of epilepsy ranged from 4 to 18 years with an average of 13.9 years. 88.3% of patients were seizure-free. The most effective drug was valproate. In eight patients drug withdrawal was attempted but all patients relapsed during a follow-up period of 1 year. Video-EEG studies were performed in eight newly diagnosed patients; myoclonic jerks were recorded in five patients.     

Smoking-responsive juvenile-onset Parkinsonism.

We describe a patient with juvenile levodopa-responsive Parkinsonism who reported a dramatic response to cigarette smoking with transient but marked improvement of motor symptoms associated with oculogyric crises and psychotic behavior. His beta-CIT single-photon emission computed tomography scan showed a complete absence of presynaptic dopaminergic nerve terminals.     

Histocompatibility antigens and post-encephalitic Parkinsonism.

Twenty-one patients with Parkinsonism secondary to von Economo's encephalitis were typed for HLA-A, B, C and DR antigens. No differences were found in the phenotype frequencies of these antigens compared with controls. This finding fails to support the hypothesis of genetic susceptibility to post-encephalitic Parkinsonism.