Late-onset oro-facial dyskinesia in Spinocerebellar Ataxia type 2: a case report.

BACKGROUND: Genetic familiar causes of oro-facial dyskinesia are usually restricted to Huntington's disease, whereas other causes are often missed or underestimated. Here, we report the case of late-onset oro-facial dyskinesia in an elderly patient with a genetic diagnosis of Spinocerebellar Ataxia type 2 (SCA2). CASE PRESENTATION: A 75-year-old man complained of progressive balance difficulty since the age of 60 years, associated with involuntary movements of the mouth and tongue over the last 3 months. No exposure to anti-dopaminergic agents, other neuroleptics, antidepressants, or other drugs was reported. Family history was positive for SCA2 (brother and the son of the brother). At rest, involuntary movements of the mouth and tongue were noted; they appeared partially suppressible and became more evident during stress and voluntary movements. Cognitive examination revealed frontal-executive dysfunction, memory impairment, and attention deficit. Brain magnetic resonance imaging (MRI) disclosed signs of posterior periventricular chronic cerebrovascular disease and a marked ponto-cerebellar atrophy, as confirmed by volumetric MRI analysis. A dopamine transporter imaging scan demonstrated a bilaterally reduced putamen and caudate nucleus uptake. Ataxin-2 (ATXN2) gene analysis revealed a 36 cytosine-adenine-guanine (CAG) repeat expansion, confirming the diagnosis of SCA2. CONCLUSIONS: SCA2 should be considered among the possible causes of adult-onset oro-facial dyskinesia, especially when the family history suggests an inherited cerebellar disorder. Additional clinical features, including parkinsonism and motor neuron disease, may represent relevant cues for an early diagnosis and adequate management.

Functional correlation between cerebellum and basal ganglia: A parkinsonism model.

INTRODUCTION: The cerebellar response has been studied for years with different models of alteration of other brain structures to understand its complex functioning and its relationship with the rest of the body. Studies in patients with Parkinson's disease (PD) showed that the cerebellar function is modified by deficit of the basal ganglia; which supports the hypothesis that both structures are related anatomically and functionally. METHODS: In our study, the ventrolateral striatum (VLS) of the basal ganglia was altered by an electrolytic lesion, in order to produce a similar jaw frequency of jaw tremor movements presented in parkinsonism, thereafter we analyzed the effect of the lesion on the expression of multiunit activity (MUA) of the cerebellum. RESULTS: We found cerebellar activation during mandibular movements and increment during oral jaw tremor movements. In addition, the amplitude of baseline MUA registered in animals with alteration of the VLS decreased with respect to the intact group. CONCLUSIONS: Accordingly, we conclude that cerebellar changes in MUA may be due to a decrease in the cerebellar inflectional or as a possible compensatory function between cerebellum and basal ganglia.

Disruption of programmed masticatory movements in unilateral MPTP-treated monkeys as a model of jaw movement abnormality in Parkinson's disease.

While motor disturbance in Parkinson's disease can affect innate, programmed processes, such as masticatory mandibular movements, the pathophysiology of such abnormalities remains unclear. This study applies digital analysis by high-speed video signal processing that tracks three dots placed around the mouth for recording masticatory movements in unilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys. The system analyzes displacement, velocity and cycle duration of the topography of mandibular movement during mastication of sweet potato slices. In monkeys receiving MPTP into the right carotid artery (n = 3), positron emission tomography indicated significant reduction in the binding of (E)-N-(3-iodoprop-2-enyl)-2ß-carbo[(11)C]methoxy-3ß-(4-methylphenyl)nortropane ([(11)C]PE2I) to the dopamine transporter in the right caudate, putamen, nucleus accumbens and substantia nigra relative to the contralateral hemisphere. These monkeys showed hypokinesia of the left forelimbs and hindlimbs. During mastication, MPTP-treated monkeys chewed preferentially on the left side, while untreated monkeys (n = 3) showed no preference for chewing side. The amplitude of vertical opening and closing movements was reduced in MPTP-treated monkeys, with a slight but significant increase in the lateral component of mandibular movements. The velocity of all phases of horizontal mandibular movements was reduced. In consequence, duration of the occlusal phase was increased, while duration of the closing phase was decreased in MPTP-treated monkeys. These findings indicate that during masticatory movements MPTP-treated monkeys chew preferentially on the side contralateral to loss of dopamine neurons, with reduced amplitude and velocity of mandibular movements. High-speed digital movement analysis is able to define and quantify abnormalities of orofacial movement topography as a sign of parkinsonism.

The broadening application of chemodenervation in X-linked dystonia-parkinsonism (Part II): an open-label experience with botulinum toxin-A (Dysport®) injections for oromandibular, lingual, and truncal-axial dystonias.

While the majority of chemodenervation clinics worldwide typically use botulinum toxins for the treatment of common conditions such as blepharopsams, cervical dystonia, limb dystonia, and spasticity, the unusually high concentration of X-linked dystonia-parkinsonism (XDP) has allowed us to collect and describe our experience in the use of botulinum toxin type A (BoNT-A) on rarer dystonic patterns. BoNT-A (Dysport®) was injected in a total 109 dystonias of XDP. Our cohort included: 50 cases in the oromandibular area (jaw opening: 32 cases, jaw closing: 12 cases, and jaw deviation: 6 cases); 35 cases in the lingual area (tongue protrusion: 27 cases and tongue curling: 8 cases); and, 24 cases in the truncal-axial area (flexor: 12 cases, extensor: 7 cases, and lateral-extensor: 5 cases). Interestingly, pain, often a nonprominent symptom of dystonias, was frequently reported in 40/50 XDP cases with oromandibular dystonia and 18/24 XDP cases with truncal-axial dystonia. All BoNT-A procedures were performed under electromyography guidance. A "high potency, low dilution" BoNT-A protocol was applied for oromandibular, lingual, cranial, cervical, and distal limb dystonias; whereas for dystonias of the abdominal, paraspinal, and proximal limb muscles, a "low potency, high dilution" BoNT-A injection protocol was applied. Outcomes measures included: the global dystonia rating scale (DRS) and pain visual analog scale (VAS) reduction at week 4; duration of BoNT-A effects; and, side effect profile. The median DRS score after 4 weeks was 3 ("substantial improvement") for oromandibular and lingual dystonias and 2 ("moderate improvement") for truncal-axial dystonias. Pain reduction was significantly reduced (75%-80% in oromandibular; 30%-80% in truncal-axial dystonias). The median duration of BoNT-A effect was 16 weeks for oromandibular, 12 weeks for lingual, and 11 weeks for truncal-axial dystonias. Compared to a generally safe and well-tolerated BoNT-A injections for truncal-axial dystonias, the oromandibular-lingual dystonias had the following frequency of adverse events: oromandibular--19% in jaw opening and 17% in jaw closing dystonias; lingual--19% in tongue protrusion and 13% in tongue curling dystonias. The most frequent adverse events were mouth dryness and dysphagia. Thus, BoNT-A injection working protocols may be adopted in XDP dystonia that adheres to cost minimization (e.g., lower dose end per selected muscle), while achieving some benefit, and potentially reduce the adverse event profile.

DNAJC6 mutation causing cranial-onset dystonia with tremor dominant levodopa non-responsive parkinsonism: A novel phenotype.

DNAJC6 mutation causes two types of phenotypes: slowly progressive parkinsonism with levodopa response and rapidly progressive parkinsonism with additional manifestations like intellectual disability, epilepsy etc. We report a new phenotype wherein an adolescent girl developed blepharospasm followed by jaw opening, lingual and cervical dystonia followed by tremors of limbs (rest and action) with rigidity, bradykinesia. The dystonia-parkinsonism phenotype has not been described. She had novel homozygous missense mutation in DNAJC6 gene.

FIG4 mutations leading to parkinsonism and a phenotypical continuum between CMT4J and Yunis Varón syndrome.

BACKGROUND: Charcot-Marie-Tooth disease type 4J (CMT4J) originates from mutations in the FIG4 gene and leads to distal muscle weakness. Two null alleles of FIG4 cause Yunis Varón syndrome with severe central nervous system involvement, cleidocranial dysmorphism, absent thumbs and halluces and early death. OBJECTIVES: To analyse the phenotypic spectrum of FIG4-related disease and explore effects of residual FIG4 protein. METHODS: Phenotyping of five new patients with FIG4-related disease. Western Blot analyses of FIG4 from patient fibroblasts. RESULTS: Next generation sequencing revealed compound heterozygous variants in FIG4 in five patients. All five patients presented with peripheral neuropathy, various degree of dysmorphism and a central nervous system involvement comprising Parkinsonism in 3/5 patients, cerebellar ataxia (1/5), spasticity of lower limbs (1/5), epilepsy (1/5) and/or cognitive deficits (2/5). Onset varied between the first and the seventh decade. There was no residual FIG4 protein detectable in fibroblasts of the four analysed patients. CONCLUSION: This study extends the phenotypic spectrum of FIG4-related disease to Parkinsonism as a feature and demonstrates new phenotypes on a continuum between CMT4J and Yunis Varón syndrome.

Polycaprolactone-based neurotherapeutic delivery of rasagiline targeting behavioral and biochemical deficits in Parkinson's disease.

Rasagiline mesylate is an irreversible MAO-B inhibitor which requires daily oral administration for treatment of Parkinson's disease due to its short half-life. Patients with Parkinson's disease also develop dysphagia, i.e., difficulty in swallowing. Encapsulating rasagiline in polycaprolactone microspheres can alleviate the problem of daily oral administration by prolonging drug release from polymeric microspheres for 1 month by single subcutaneous administration. Polycaprolactone shows absence of any acidic environment generation during its degradation in body which is its advantage over poly (lactic-co-glycolic) acid. Exploiting pH-based solubility of rasagiline mesylate pH changes during microencapsulation process was performed to fabricate rasagiline mesylate-loaded polycaprolactone microspheres. Particle size analysis of microspheres showed mean particle size range of 24.18-47.87 µm. Scanning electron micrographs revealed spherical non-porous particles with small pits and depressions on the surface. In vitro release studies of formulations were performed to get an idea about in vivo behavior of prepared formulations. Stereotaxic rotenone model was used to study in vivo efficacy of formulation in rats. Selected formulation significantly (p < 0.05) improved various behavioral (locomotor activity, grip strength, etc.) and biochemical (lipid peroxidation, reduced glutathione, etc.) changes. Polymeric microspheres showed robust effect on all outcomes assessed with non-significant difference between daily administration of rasagiline mesylate solution and drug-loaded polymeric microspheres administered once in a month. With prepared controlled release injectable once a month, administration is required making it an interesting and convenient approach in treatment of Parkinson's disease with dysphagia. Patient compliant system can be achieved by exploiting this approach for future use.

Primitive reflexes distinguish vascular parkinsonism from Parkinson's disease.

OBJECTIVES: Although vascular parkinsonism (VP) occurs frequently in the elderly, its clinical features have not been investigated in detail, particularly in comparison with Parkinson's disease (PD). The goal of this study is to clarify the diagnostic value of pathological reflexes in differentiating between VP and PD. PATIENTS AND METHODS: In 132 patients with PD and 55 with VP, pathological reflexes, including snout reflex (SR), palmomental reflex (PMR), corneomandibular reflex (CMR), jaw reflex (JR), Hoffmann reflex (HR), and extensor plantar response (EPR), were evaluated. RESULTS: The percentage of each pathological reflex elicited in two groups (VP:PD) was as follows: SR (78:30), PMR (53:26), CMR (9:6), JR (33:12), HR (29:11), and EPR (25:8). The prevalence of pathological reflexes, except for CMR, was significantly higher in the VP patients than in the PD patients. In particular, SR and PMR were more frequent than upper motor neuron signs in the VP patients. The sensitivity and specificity of either SR or PMR for VP were 84% and 82%. CONCLUSION: Snout and palmomental reflexes are useful tools in the differentiation between VP and PD.

The muscarinic receptor antagonist tropicamide suppresses tremulous jaw movements in a rodent model of parkinsonian tremor: possible role of M4 receptors.

RATIONALE: Nonselective muscarinic acetylcholine antagonists have been used for several years as antiparkinsonian drugs. However, there are at least five subtypes of muscarinic receptor (M1-5). Neostriatal M4 receptors have been implicated in aspects of motor function, and it has been suggested that M4 antagonists could be used as treatments for parkinsonism. OBJECTIVE: Currently, there is a lack of highly selective M4 antagonists that readily penetrate the blood brain barrier. Thus, the present studies focused upon the effects of tropicamide, a muscarinic acetylcholine receptor antagonist with moderate binding selectivity for the M4 receptor subtype. MATERIALS AND METHODS: Tremulous jaw movements were used as a model of parkinsonian tremor in these studies, and the effects of tropicamide were compared with those of the nonselective muscarinic antagonist atropine. RESULTS: Tropicamide suppressed the tremulous jaw movements induced by the muscarinic agonist pilocarpine and the dopamine antagonist pimozide. Analysis of the dose-response curves indicated that tropicamide showed approximately the same potency as atropine for suppression of pilocarpine-induced jaw movements but was more potent than atropine on the suppression of pimozide-induced jaw movements. In contrast, atropine was more potent than tropicamide in terms of impairing performance on visual stimulus detection and delayed nonmatch-to-position tasks. CONCLUSIONS: These studies demonstrate that tropicamide, which currently is used clinically for ophthalmic purposes, can exert actions that are consistent with antiparkinsonian effects. Moreover, the different pattern of effects shown by tropicamide compared to those of atropine on motor vs cognitive tasks could be due to the modest M4 selectivity shown by tropicamide.

Taste in dementing diseases and parkinsonism.

Like with many sensory abilities a reduction of taste and smell occurs during aging. Since there are hints to an additional reduction in dementing diseases, we assessed 52 patients, 26 women and 26 men, who were presented to a memory clinic, using the Sniffin' Sticks, Whole Mouth and Taste Strip Tests. While smoking, alcohol consumption, intake of drugs and sex exerted only minor impact, age and the severity of cognitive impairment were of major importance. There was a moderate but significant correlation between the severity of dementia, taste and smell, even if the age effect was partialled out. Notably, patients with Parkinson syndrome showed worse taste and smell abilities than those without. Here the differences were indeed marked enough to play a possible role in making the diagnosis. This exploratory study confirms a mild reduction of gustatory function in dementing diseases over and beyond that of normal aging which--in addition to a reduction of smell--seems to be especially marked in Parkinson syndromes.

A novel skilled-reaching impairment in paw supination on the "good" side of the hemi-Parkinson rat improved with rehabilitation.

Parkinson's disease is characterized by tremor, rigidity, bradykinesia, and postural abnormalities ascribed to the loss of nigrostriatal dopamine (DA). Symptoms similar to the human condition can be produced in the rat by DA-depleting 6-hydroxydopamine injections made into the nigrostriatal system. After a unilateral lesion, the rat symptoms include sensory and motor impairments and turning biases reflecting motor abnormalities to the contralateral-to-depletion side of the body. In addition, a number of studies on skilled reaching report impairments in the use of the ipsilateral limb. It is suggested that the ipsilateral deficit is secondary to the contralateral motor impairments however. Here we re-examine how rats with unilateral DA depletion use their ipsilateral limb for skilled reaching for food. We provide the first description of an impairment on the ipsilateral-to-depletion side of the body of the rat and the first demonstration of amelioration of the defect using behavioral therapy. Video analysis of rats reaching for single pellets of food with the ipsilateral limb revealed that, although limb advancement and food grasping were normal, paw supination and food release to the mouth were impaired. Consequently, the animals were unable to transport a grasped food pellet to the mouth. Behavioral therapy, consisting of training in a simpler reaching task, strikingly lessened the impairment and improved reaching movements to the point that the rats could transport the food to the mouth. The results are discussed in relation to possible causes of the ipsilateral impairment, its treatment, and to relevant research on human Parkinson patients, indicating that they display bilateral improvements after unilateral treatments.

Dopamine agonists suppress cholinomimetic-induced tremulous jaw movements in an animal model of Parkinsonism: tremorolytic effects of pergolide, ropinirole and CY 208-243.

Considerable evidence indicates that cholinomimetic-induced tremulous jaw movements in rats share many characteristics with human Parkinsonian tremor, and several antiparkinsonian drugs suppress cholinomimetic-induced tremulous jaw movements. The present study investigated three different types of dopamine agonists, which have known antiparkinsonian characteristics, for their ability to suppress the tremulous jaw movements induced by tacrine (5.0 mg/kg). The non-selective dopamine agonist pergolide, a widely used antiparkinsonian drug, was highly potent at suppressing tacrine-induced jaw movements (e.g. 0.125-1.0 mg/kg). The selective D2 agonist ropinirole, which also is used clinically as an antiparkinsonian drug, suppressed jaw movements in the dose range of 2.5-20.0 mg/kg. The D1 agonist CY 208-243, which has been reported to suppress tremor, also reduced jaw movement activity (4.0 mg/kg). Across several studies, the rank order of potency for suppressing cholinomimetic-induced jaw movements in rats is related to the potency for producing antiparkinsonian effects in humans. Together with previous studies, the present results suggest that cholinomimetic-induced jaw movements in rats can be used to characterize dopaminergic antiparkinsonian agents and to investigate the basal ganglia circuits involved in the generation of tremulous movements.

Adenosine A2A receptor-mediated control of pilocarpine-induced tremulous jaw movements is Parkinson's disease-associated GPR37 receptor-dependent.

GPR37, also known as parkin associated endothelin-like receptor (Pael-R), is an orphan GPCR that aggregates intracellularly in a juvenile form of Parkinson's disease. However, little is known about the function of this orphan receptor. Here, using a model for parkisonian tremor, the pilocarpine-induced tremulous jaw movements (TJMs), we show that the deletion of GPR37 attenuated the TJMs in response to this cholinomimetic. Interestingly, the control that adenosine A2A receptor exerted over TJMs was lost in the absence of GPR37, thus pointing to a pivotal role of this orphan receptor in the adenosinergic control of parkinsonian tremor.

Local injections of the 5-hydroxytryptamine antagonist mianserin into substantia nigra pars reticulata block tremulous jaw movements in rats: studies with a putative model of Parkinsonian tremor.

RATIONALE: Atypical antipsychotics such as clozapine and olanzapine have a low liability for producing motor side effects. In addition to being D2 antagonists, these drugs have a complex binding profile that includes affinity for muscarinic, alpha, H1, and various serotonin receptors. Previous work in rats has shown that atypical antipsychotics suppress tremulous jaw movements induced by the anticholinesterase tacrine in rats. Cholinomimetic-induced jaw movements are a putative model of parkinsonian tremor, and the ability of antipsychotic drugs to suppress these movements in rats is correlated with motor side-effect liability in humans. OBJECTIVE: The present work was undertaken to study the role of central serotonin receptors in the generation of cholinomimetic-induced jaw movements. RESULTS: Systemic injections of the serotonin antagonist mianserin suppressed tacrine-induced jaw movements, with an ED(50) of 2.77 mg/kg. Local injections of mianserin directly into substantia nigra pars reticulata (SNr) also suppressed tacrine-induced jaw movements. Injections into ventrolateral neostriatum, or a control site dorsal to SNr, failed to have any effects on jaw movement activity. CONCLUSIONS: These studies suggest that atypical antipsychotics may act both on striatal muscarinic receptors and nigral serotonin receptors to suppress jaw movement activity. It is possible that the unique motor properties of atypical antipsychotics result from actions on multiple receptors in several brain areas. The precise serotonin receptor subtype involved in these effects is unknown, and future work will examine the effects of drugs that act selectively on 5-HT(2A) and 5-HT(2C) receptors.

The adenosine A2A antagonist KF17837 reverses the locomotor suppression and tremulous jaw movements induced by haloperidol in rats: possible relevance to parkinsonism.

Recent evidence indicates that adenosine A2A receptors modulate the activity of striatal neurons, and that antagonists of this receptor may have actions in various animal models related to motor function. Four experiments were conducted to study the effects of systemic injections of the adenosine A2A antagonist KF17837 on the behavioral effects produced by repeated administration of the dopamine (DA) antagonist haloperidol. In the first two experiments, it was shown that repeated 0.5 mg/kg haloperidol severely suppressed open-field locomotor activity, and that KF17837 (0.0-20.0 mg/kg) did not significantly increase open-field locomotor activity. The third experiment demonstrated that injections of KF17837 (0.0-20.0 mg/kg) completely reversed the suppression of locomotion induced by haloperidol, and also increased rearing behavior in haloperidol-treated rats. Previous research has reported that haloperidol induces tremulous jaw movements that have many of the characteristics of parkinsonian tremor. The fourth experiment demonstrated that i.p. injections of KF17837 (0.0-20.0 mg/kg) also suppressed haloperidol-induced tremulous jaw movements. Taken together, the results of these experiments indicate that adenosine A2A antagonism can reverse the locomotor suppression and tremulous movements induced by DA antagonism. This profile of activity is consistent with the hypothesis that antagonism of adenosine A2A receptors can result in an antiparkinsonian effect in animal models.

Neostriatal muscarinic receptor subtypes involved in the generation of tremulous jaw movements in rodents implications for cholinergic involvement in parkinsonism.

Several studies have shown that a number of pharmacological and neurochemical conditions in rats can induce jaw movements that are described as "vacuous" or "tremulous". For several years, there has been some debate about the clinical significance of various drug-induced oral motor syndromes. Nevertheless, considerable evidence now indicates that the non-directed, chewing-like movements induced by cholinomimetics have many of the characteristics of parkinsonian tremor. These movements are characterized largely by vertical deflections of the jaw, which occur in the same 3-7 Hz peak frequency that is typical of parkinsonian tremor. Cholinomimetic-induced tremulous jaw movements are suppressed by a number of different antiparkinsonian drugs, including scopolamine, benztropine, L-DOPA, apomorphine, bromocriptine, ropinirole, pergolide, amantadine, diphenhydramine and clozapine. A combination of anatomical and pharmacological research in rats has implicated M4 receptors in the ventrolateral neostriatum in the generation of tremulous jaw movements. Mice also show cholinomimetic-induced jaw movements, and M4 receptor knockout mice demonstrate subtantially reduced levels of jaw movement activity, as well as increased locomotion. Taken together, these data are consistent with the hypothesis that a centrally-acting M4 antagonist may be useful as a treatment for parkinsonian symptoms, including tremor.

Physiologic assessment of autonomic dysfunction in pallidopontonigral degeneration with N279K mutation in the tau gene on chromosome 17.

Autonomic function was investigated in five affected and five at-risk members of a single kinship of pallidopontonigral degeneration (PPND), which is a progressive syndrome of parkinsonism and frontotemporal dementia resulting from a mutation in the N279K tau gene on chromosome 17. Affected subjects reported symptoms including hyperhidrosis, sialorrhea, urinary frequency or incontinence, thermal intolerance, male sexual dysfunction, lacrimation, and dryness of the eyes or mouth. None had orthostatic hypotension. Autonomic testing revealed mild-to-moderate abnormalities in all five affected subjects and minor abnormalities in the three oldest, asymptomatic, at-risk subjects. Findings in affected subjects consisted of preganglionic sudomotor dysfunction in all five, impaired cardiovagal function in three, and reduced or absent pupillary near responses in four. Tests of adrenergic function were normal in all subjects. The degree of autonomic dysfunction correlated significantly with disease duration and with indices of disease severity. In conclusion, there is evidence in PPND of a disturbance in the central autonomic network.

[Juvenile parkinsonism with symmetrical hypoperfusion in the cerebellum--a case report].

We report a 24-year-old female presenting levodopa-responsive juvenile parkinsonism with symmetrical hypoperfusion in the cerebellum. At the age of 21, she noticed difficulty in brushing her teeth and writing with the right hand. She developed resting tremor in the right hand. These symptoms were dramatically relieved by levodopa. One year prior to the admission, she noticed dystonia and drug-induced motor fluctuations and her symptoms became worse. Neurological examinations disclosed resting and postural tremor in both hands and the right leg. Bradykinesia and cogwheel rigidity were noted on the right side. Deep tendon reflexes were slightly increased on the right side, while Babinski sign was negative. Slight lateropulsion was observed without retropulsion. Sensory, autonomic and cerebellar disturbances were not observed. No abnormalities were found in parkins gene or in the genes of spinocerebellar ataxia (SCA) 1,2,3,6,7,8 and alpha-synuclein. Cranial CT scan and brain MRI were normal, but technetium-99m ethyl cysteinate dimer (ECD) single photon emission computed tomography (SPECT) showed symmetrical hypoperfusion in the cerebellum. Other 5 patients presenting juvenile parkinsonism and 10 aged-matched normal controls in our hospital did not show hypoperfusion in the cerebellum on ECD SPECT. Cerebellar blood flow has not been measured in the previously reported cases of juvenile parkinsonism. These results suggested that etiopathogenesis in this patient was different from that in previously reported cases.

Assessing speech dysfunction using BOLD and acoustic analysis in parkinsonism.

INTRODUCTION: Speech dysfunction is often associated with parkinsonism (Parkinson's disease (PD), Multiple System Atrophy (MSA), and Progressive Supranuclear Palsy (PSP)), along with characteristic motor features. Any or all of the following i.e. respiratory, phonatory, resonatory, or articulatory components of speech production may be affected. Articulatory imprecision, repetition of syllables (tachyphrenia), and tremor of oropharyngeal structures add to speech unintelligibility. We studied acoustics using spectrogram and its correlation with BOLD activation during voice/speech production across these subjects. METHODS: BOLD studies were conducted on 108 subjects (29 PD, 20 MSA and 19 PSP and 40 controls) on 1.5 T MR scanner using 130 dynamics. Active phase involved acquisition (10 volumes each) of audible reading of visually presented bi-syllabic meaningful Hindi simple words (5 types of non-nasal stop consonant categories, i.e. namely velars, palatals, retroflexes, dentals, bilabials and one nasal stop consonant) with interleaved silence during baseline. The subjects' voice samples were analyzed for acoustic parameters, namely formant frequencies of the adjoining vowels, voice onset time (VOT), and intensities using spectrogram. Correlation of BOLD activation in different brain areas with acoustic parameters was evaluated. RESULTS: Voice intensity was significantly lowered, while VOTs were delayed in these patients as compared to healthy controls. All acoustic parameters were significantly affected for nasal consonants. BOLD activation correlated positively in primary motor cortex to VOTs, while F2 formants to activation of supplementary motor area. CONCLUSION: The differences in the acoustic quality of various stop consonants in patients may be helpful in differentiating these three parkinsonian disorders.