Diffusion tensor imaging of Parkinson's disease,atypical parkinsonism,and essential tremor

Diffusion tensor imaging could be useful in characterizing movement disorders because it noninvasively examines multiple brain regions simultaneously. We report a multitarget imaging approach focused on the basal ganglia and cerebellum in Parkinson's disease, parkinsonian variant of multiple system atrophy, progressive supranuclear palsy, and essential tremor and in healthy controls. Seventy‐two subjects were studied with a diffusion tensor imaging protocol at 3 Tesla. Receiver operating characteristic analysis was performed to directly compare groups. Sensitivity and specificity values were quantified for control versus movement disorder (92% sensitivity, 88% specificity), control versus parkinsonism (93% sensitivity, 91% specificity), Parkinson's disease versus atypical parkinsonism (90% sensitivity, 100% specificity), Parkinson's disease versus multiple system atrophy (94% sensitivity, 100% specificity), Parkinson's disease versus progressive supranuclear palsy (87% sensitivity, 100% specificity), multiple system atrophy versus progressive supranuclear palsy (90% sensitivity, 100% specificity), and Parkinson's disease versus essential tremor (92% sensitivity, 87% specificity). The brain targets varied for each comparison, but the substantia nigra, putamen, caudate, and middle cerebellar peduncle were the most frequently selected brain regions across classifications. These results indicate that using diffusion tensor imaging of the basal ganglia and cerebellum accurately classifies subjects diagnosed with Parkinson's disease, atypical parkinsonism, and essential tremor and clearly distinguishes them from control subjects. © 2013 International Parkinson and Movement Disorder Society     

Post-encephalitic tremor and delayed-onset parkinsonism

Movement disorders of various types may occur in relation to viral infections of the central nervous system. They manifest themselves as obvious signs at clinical onset or during the acute phase of an encephalitis (myoclonus, tremor, or parkinsonism), or appear as later sequelae decades after the illness. We describe here a man who developed an unusual movement disorder after a probable viral encephalitis in his childhood. This consisted of a tremor (3-4Hz frequency and 100-150ms duration) of the neck, left shoulder and arm, which persisted unchanged during the ensuing years. The patient regarded this abnormal movement as annoying, but otherwise it did not impair his lifestyle. He subsequently developed the clinical picture of parkinsonism many decades after the onset of tremor, and we speculate that both tremor and parkinsonism can be considered sequelae of encephalitis, but each with a different time-course. The left-sided jerky tremor was an immediate sequela in the childhood; whereas, the rigid-akinetic parkinsonian picture represented a later sequela of the infection in old age. The injured site responsible for both the segmental tremor and the parkinsonism presumably involved the brainstem.     

Dopa-responsive pseudo-orthostatic tremor in parkinsonism.

In four patients an inabilitating standing tremor appeared years before that parkinsonian symptoms were evidenced. This tremor was refractory to gabapentin and dramatically responded to Levodopa administration. Its dominant frequency was 6.2 to 6.9 Hz with sporadic subharmonics at 8 to 18 Hz. Three patients were affected by different genetic mutations (Park 2, Park 6, mtDNA deletion) in one no genetic or metabolic alterations could be evidenced. All patients had dopamine transporter abnormalities. We suggest that the term "Pseudo-Orthostatic Tremor" could be used to define this Dopa responsive, 6 to 7 Hz standing tremor.     

MRI for the differential diagnosis of neurodegenerative parkinsonism in clinical practice

Parkinson's disease (PD) is the most common neurodegenerative cause of parkinsonism, followed by progressive supranuclear palsy (PSP) and multiple system atrophy (MSA). Despite the publication of consensus operational criteria for the diagnosis of PD and the various atypical parkinsonian disorders (APD) such as PSP, MSA and corticobasal degeneration, an accurate diagnosis of neurodegenerative parkinsonian syndromes remains a challenge for each neurologist. Particularly in the early disease stages the clinical separation of APDs from PD carries a high rate of misdiagnosis. However, an early differentiation between APD and PD, each characterized by completely different natural histories, is crucial for determining the prognosis and choosing a treatment strategy. MRI plays an important role in the exclusion of symptomatic parkinsonism due to other pathologies. Over the past two decades, conventional MRI and advanced MRI techniques, including proton magnetic resonance spectroscopy (1H-MRS), diffusion-weighted imaging (DWI), magnetization transfer imaging (MTI), and magnetic resonance volumetry (MRV) have shown abnormalities in the substantia nigra and basal ganglia, especially in APD. Furthermore, in accordance with neuropathological studies suggesting that the olfactory system is an early target of the disease, recent studies using advanced MRI techniques have shown abnormalities in the olfactory system in the early disease stages of patients with PD. Given that olfactory deficits may be a premotor marker of the disease, such methods may eventually evolve into an early screening tool for PD.     

Differential diagnosis of tremor syndromes using MRI relaxometry

Differential diagnosis of the most common tremor syndromes – essential tremor (ET) and Parkinson's disease (PD) is burdened with high error rate. However, diagnostic MRI biomarkers applicable in this clinically highly relevant scenario remain an unfulfilled objective.The presented study was designed in search for possible candidate MRI protocols relevant for differential diagnostic process in tremor syndromes.10 non-advanced tremor-dominant PD patients meeting diagnostic criteria for clinically established PD, 12 isolated ET patients and 16 healthy controls were enrolled into this study. The study focused on relaxation MRI protocols – T1, T2, adiabatic T1ρ and adiabatic T2ρ due to their relatively low post-processing requirements enabling implementation into routine clinical practice.Compared to ET, PD patients had significantly longer T2 relaxation times in striata with dominant findings in the putamen contralateral to the clinically more affected body side. This difference was driven by alterations in the PD group as confirmed in the complementary comparison with healthy controls. According to the receiver operating characteristic analysis, this region provided a reasonable sensitivity of 0.91 and specificity of 0.89 in the differential diagnosis of PD and ET. In PD patients, we further found prolonged T1ρ in the substantia nigra compared to ET and healthy controls, and shorter T2 and T2ρ in the cerebellum compared to healthy controls.T2 relaxation time in the putamen contralateral to the clinically more affected body side is a plausible candidate diagnostic marker for the differentiation of PD and ET.     

A case of orthostatic tremor in parkinsonism

A 79-year-old woman presenting with orthostatic tremor (OT) was reported. In addition to OT, neurological examination showed mild dementia, bradykinesia, rigidity of the neck and the upper limbs and positive Babinski reflex on the left. These clinical signs and CT as well as MRI findings suggested vascular parkinsonism as its pathological background. Upon standing with her feet together, she rapidly developed rhythmic repetitive contraction of all leg muscles. The shaking disappeared by walking, sitting, or lying down. The EMG recording revealed 4-Hz tremor which consisted of alternating contraction of anti-gravity muscles and their antagonists. The EMG bursts associated with the tremor were synchronous in corresponding muscles of both legs. OT could be bilaterally reset by unilateral voluntary or passive movement of leg. In the supine position, the tremor was not evoked by voluntary contraction of leg muscles against resistance. As the tremor was aggravated by the administration of haloperidol was suppressed by L-DOPA, it was thought to have the pharmacological basis common to the resting tremor of parkinsonism. Furthermore, we postulated that the postural tonus-regulating system, which is thought to set and maintain the tonus of antigravity muscles for standing upright, might be involved in the generation of the rhythmic discharge pattern (reciprocal bursts in a given leg and synchronized bursts in both legs) of OT.     

Prospective evaluation of parkinsonism and tremor in patients treated with valproate

We observed a high incidence of postural and intentional tremor in patients exposed to VPA, although not strong enough to interfere with normal life. l-dopa unresponsive parkinsonism was recorded in 10% of patients who received VPA treatment. No correlation with gender, dosage, duration of treatment or concomitant administration of other antiepileptic drugs was observed. The mechanisms for such side effects are unclear. As new GABA mimetic drugs have been postulated to be useful in tremor control [8], it remains paradoxical that VPA should exacerbate such symptomatology by means of a similar mechanism of action.     

MRI volumetric morphometry in vascular parkinsonism

Journal of Neurology - Vascular parkinsonism is a difficult clinical differential diagnosis in elderly subjects. We aimed at identifying morphometric markers in the brain of elderly patients with...     

Cinnarizine-induced parkinsonism. Susceptibility related to aging and essential tremor

Age at onset in 24 consecutive cinnarizine-induced parkinsonism (CIP) patients referred during a 2-year period was compared with 102 newly referred cases of Parkinson's disease (PD) examined during the same period. Not only did CIP onset occur at a greater age than PD (70.6 + 1.4 years versus 60.1 + 1.1 years), but the number of CIP cases increased steadily with age, whereas the incidence of PD patients peaked between the ages of 55 and 60 years, as is usually the case. At the time of referral, 62% of CIP cases and 14% of PD cases were over the age of 70, suggesting that advanced age was not a source of referral bias. A structured questionnaire prospectively given to 24 CIP patients revealed a history of tremor in at least one family member in 56% of the cases, whereas the incidence was much lower in 124 PD cases (17%) and 102 hospitalized nonneurological patients aged over 65 (6%). Moreover, three of the CIP patients themselves had a history of essential tremor previous to the onset of parkinsonism. CIP patients had frequently been exposed to the drug for years before developing any extrapyramidal symptoms (mean exposure, 4.1 +/- 4 years; range 4 months to 15 years). Though controlled epidemiological studies are needed to evaluate the possibility that cinnarizine is increasingly prescribed in the general population with advancing age, our data suggests that aging plus a background of genetically determined essential tremor represented critical risk factors for development of this drug side effect.     

Effect of clonidine and atropine on rest tremor in the MPTP monkey model of parkinsonism

The purported alpha 2-adrenergic agonist clonidine was found to inhibit rest tremor at doses of 0.023-0.1 mg/kg in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine monkey model of parkinsonism. The effect was dose dependent, but sedation and reduced mobility were observed. Atropine at doses of 0.1-1 mg/kg also reduced tremor in a dose-dependent fashion, but side-effects in the form of agitation, dilated pupils, and dry mouth were seen. When the two drugs were combined, however, we saw a significant potentiation of the antitremor effect. We could even abolish tremor with doses of atropine and clonidine that by themselves were without effect. The side-effects were almost eliminated by the combination.     

Arylsulphatase A (ASA) activity in parkinsonism and symptomatic essential tremor

Arylsulphatase A (ASA) activity was evaluated in 47 patients with a diagnosis of parkinsonism or essential tremor. Mean ASA activity was significantly reduced compared with both a healthy control group of 71 individuals (p < 0.01) and with a group of 44 neurological patients without movement disorders (p < 0.02). Using definite clinical criteria the patients were classified as typical or atypical with respect to Parkinson's disease (PD) or essential tremor (ET). A normal ASA level was found in all the cases showing typical clinical features (PD and ET), while ASA activity was significantly lowered (p < 0.01) in 55.6% of the atypical cases (Parkinsonian syndrome or symptomatic ET). Our data support the hypothesis of a non-casual association between low ASA level and the clinical features of parkinsonism or symptomatic ET.     

震颤分析在帕金森病和原发性震颤鉴别诊断中的应用

目的 探讨震颤分析在帕金森病(parkinson's disease,PD)和原发性震颤(essential trem-or,ET)鉴别诊断中的应用价值.方法 选取2017年9月至2020年11月在福建省立金山医院门诊和住院确诊的PD患者27例(PD组)和ET患者23例(ET组),所有患者均至少有一侧上肢静止性或姿势性...     

Evolving resting head tremor in parkinsonism: Clinicopathological study of a case

IntroductionResting limb tremor (RLT) is a well known feature in parkinsonism. There is very little information on resting head tremor (RHT) in parkinsonism, and none in pathologically confirmed cases. The association between RLT and RHT remains uncertain.MethodsA Caucasian male developed upper limb tremor and voice changes at age 70. He was first assessed at our clinic at age 72. At age 73 he developed resting head tremor (RHT) which prevented him from falling asleep. His status was documented in longitudinal follow-up at our clinic. He had a total of 14 clinical evaluations and four videos made over 6 years. Autopsy of the brain and spinal cord was performed.ResultsThe resting head tremor improved on antiparkinsonian drugs and resolved completely after four years. Coincident with RHT remission, the upper limb tremor worsened and interfered with feeding, and his lower limb resting tremor became more pronounced. During his course he developed slow, scanning speech and all the cardinal motor findings of parkinsonism. There was no ophthalmoplegia. Post-mortem neuropathological examination revealed prominent progressive supranuclear palsy (PSP) changes and minor Lewy body pathology.ConclusionThis is the first autopsy confirmed case of parkinsonism with RHT. He had dual pathology. Dissociation between RHT and RLT indicates that the oscillatory brain centers for the two were different in this case.     

Apomorphine in the diagnosis and treatment of parkinsonian tremor

The response of rest tremor to single doses of subcutaneous apomorphine and oral levodopa was compared in 20 patients with tremor-dominant Parkinson's disease. In eight of these patients, who were experiencing refractory levodopa-induced fluctuations characterised by disabling tremor, we studied the efficacy of sustained subcutaneous apomorphine. Nineteen patients responded favourably to acute challenges of both apomorphine and levodopa, with abolition of tremor in 10. In three, the response was helpful in confirming the clinical diagnosis. Chronic apomorphine use led to a more than 50% reduction in tremor-filled hours per day. After a mean duration of follow-up of 7.5 months, there was no tachyphylaxis to its therapeutic action. Subcutaneous apomorphine is an effective adjunct in treating patients with resistant, tremor-dominant fluctuations, and may also be helpful in the diagnosis of parkinsonian tremor.     

Visual hallucinations in the differential diagnosis of parkinsonism

Visual hallucinations (VH) occur commonly in Parkinson's disease (PD) and dementia with Lewy bodies (DLB) but are reported much less frequently in other neurodegenerative causes of parkinsonism, such as progressive supranuclear palsy, multiple system atrophy and corticobasal degeneration syndrome. This clinical sign may be helpful when considering the differential diagnosis of patients with parkinsonism. The observation that VH may be specific to Lewy body pathology probably reflects a greater vulnerability of the visual systems to PD and DLB neurodegeneration compared with other diseases. Topographic differences in pathology are probably the major factor producing VH in Lewy body diseases, rather than neurophysiological changes that are specific to α-synuclein protein accumulation. VH correlate with pathology in the limbic system and more specifically the amygdale that is frequently affected in PD and DLB but relatively preserved in other forms of parkinsonism often misdiagnosed as PD. In this review, the published frequencies of VH in these different conditions are compared to put into context the notion of VH as a clinical clue to underlying Lewy body pathology.