Novel hyperkinetic dystonia-like manifestation and neurological disease course of Swedish Gaucher patients

Machaczka, Maciej; Paucar, Martin; Björkvall, Cecilia Kämpe; Smith, Nicholas J.; Cox, Timothy M.; Forsgren, Lars; Svenningsson, Per

doi:10.1016/j.bcmd.2016.10.011

Cited by 21 publications

(20 citation statements)

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“…Furthermore, the patient phenotypes ranged from death in early childhood, to autism, to successful college students, implicating the role of genetic modifiers [2]. Even among Norrbottnian patients who share genotype L444P/L444P, significant clinical variation has been reported [18]. …”

Section: Genotype–phenotype Correlation In Gaucher Diseasementioning

confidence: 99%

“…Symptoms seen with this form of the disorder include hematological and visceral symptoms, as well as a horizontal supranuclear gaze palsy with skeletal involvement, often including a gibbus deformity. Other manifestations include a convergent squint (due to abducens nerve palsy), retinal infiltrates, ataxia, mild spasticity in the legs, epilepsy (myoclonic or complex partial seizures), and a slow cognitive decline into dementia [18]. …”

Section: Genotype–phenotype Correlation In Gaucher Diseasementioning

confidence: 99%

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The Spectrum of Neurological Manifestations Associated with Gaucher Disease

Lal

Sidransky

2017

Diseases

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Gaucher disease, the most common lysosomal storage disorder, is due to a deficiency in the enzyme glucocerebrosidase. This leads to the accumulation of its normal substrate, glucocerebroside, in tissue macrophages, affecting the hematological, visceral, bone and neurologic systems. Gaucher disease is classified into three broad phenotypes based upon the presence or absence of neurological involvement: type 1 (non-neuronopathic), type 2 (acute neuronopathic), and type 3 (subacute neuronopathic). Phenotypically, there is a wide spectrum of visceral and neurological manifestations. Enzyme replacement is effective in managing the visceral disease; however, treating the neurological manifestations has proved to be more challenging. This review discusses the various neurological manifestations encountered in Gaucher disease, and provides a brief overview regarding the treatment and ongoing research challenges.

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Section: Genotype–phenotype Correlation In Gaucher Diseasementioning

confidence: 99%

Section: Genotype–phenotype Correlation In Gaucher Diseasementioning

confidence: 99%

The Spectrum of Neurological Manifestations Associated with Gaucher Disease

Lal

Sidransky

2017

Diseases

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“…Despite the same genetic cause, the clinical course of the disease differs between individuals. The symptom burden is highly variable and can include horizontal supranuclear gaze palsy, ataxia, spastic paresis, cognitive impairment, and seizures (4). Enzyme replacement therapy is effective concerning the hematological and visceral manifestations.…”

Section: Introductionmentioning

confidence: 99%

Saccadic Impairments in Patients with the Norrbottnian Form of Gaucher’s Disease Type 3

et al. 2017

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BackgroundChronic neuronopathic Gaucher’s disease type 3 (GD3) is relatively frequent in northern Sweden. Besides multiple other neurological symptoms, horizontal gaze palsy or oculomotor apraxia is common in GD3.ObjectiveTo characterize the saccades in patients with Norrbottnian GD3 with respect to their neurological and cognitive status using a computer-based eye-tracking technique.MethodsHorizontal and vertical reflexive saccades as well as antisaccades of nine GD3 patients [4M/5F; 41.1 ± 11.0 years; modified severity scoring tool (mSST): 9.3 ± 5.4; Montreal Cognitive Assessment (MoCA): 24.0 ± 4.2] and age-matched controls were analyzed using EyeBrain T2, a head-mounted binocular eye tracker. Systematic clinical assessment included the mSST, a valid tool for monitoring the neurological progression in GD3 and MoCA.ResultsIn Norrbottnian GD3 patients, gain, peak, and average velocity (107.5°/s ± 41.8 vs. 283.9°/s ± 17.0; p = 0.0009) of horizontal saccades were reduced compared to healthy controls (HCs). Regarding vertical saccades, only the average velocity of downward saccades was decreased (128.6°/s ± 63.4 vs. 244.1°/s ± 50.8; p = 0.004). Vertical and horizontal saccadic latencies were increased (294.3 ms ± 37.0 vs. 236.5 ms ± 22.4; p = 0.005) and the latency of horizontal reflexive saccades was correlated with the mSST score (R2 = 0.80; p = 0.003). The latency of antisaccades showed association to MoCA score (R2 = 0.70; p = 0.009). GD3 patients made more errors in the antisaccade task (41.5 ± 27.6% vs. 5.2 ± 5.8%; p = 0.005), and the error rate tended to correlate with the cognitive function measured in MoCA score (p = 0.06).ConclusionThe mean age of 41 years of our GD3 cohort reflects the increased life expectancy of patients in the Norrbottnian area compared to other GD3 cohorts. Marked impairment of horizontal saccades was evident in all patients, whereas vertical saccades showed distinct impairment of downward velocity. Latency of reflexive saccades was associated with the severity of neurological symptoms. Increased latency and error rate in the antisaccade task were linked to cognitive impairment. The assessment of saccades provides markers for neurological and neuropsychological involvement in Norrbottnian GD3.

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“…Clinical parameters, such as the degree of cervical dystonia, did not predict olfactory decline. Non-motor manifestations of dystonia, such as cognitive and psychiatric alterations, which potentially impact the performance of olfactory tests [ 161 , 164 , 168 , 169 , 170 , 171 , 172 , 173 , 174 , 175 , 176 , 177 , 178 , 179 ], were not assessed as co-factors in this study.…”

Section: Olfactory Deficits In Dystonia: the Current Statementioning

confidence: 99%

“…There are few reports on olfaction in subjects with combined dystonia, such as Lubag syndrome [ 174 , 175 ], spinocerebellar ataxia type 3 [ 176 ], and neuronopathic Gaucher [ 177 ]. Mild to moderate olfactory decline was found in these subjects [ 174 , 175 , 176 , 177 ]. The results are not reviewed in detail here because the pathophysiology of these combined dystonia syndromes may be different from primary dystonia.…”

Section: Olfactory Deficits In Dystonia: the Current Statementioning

confidence: 99%

Olfaction as a Marker for Dystonia: Background, Current State and Directions

et al. 2020

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Dystonia is a heterogeneous group of hyperkinetic movement disorders. The unifying descriptor of dystonia is the motor manifestation, characterized by continuous or intermittent contractions of muscles that cause abnormal movements and postures. Additionally, there are psychiatric, cognitive, and sensory alterations that are possible or putative non-motor manifestations of dystonia. The pathophysiology of dystonia is incompletely understood. A better understanding of dystonia pathophysiology is highly relevant in the amelioration of significant disability associated with motor and non-motor manifestations of dystonia. Recently, diminished olfaction was found to be a potential non-motor manifestation that may worsen the situation of subjects with dystonia. Yet, this finding may also shed light into dystonia pathophysiology and yield novel treatment options. This article aims to provide background information on dystonia and the current understanding of its pathophysiology, including the key structures involved, namely, the basal ganglia, cerebellum, and sensorimotor cortex. Additionally, involvement of these structures in the chemical senses are reviewed to provide an overview on how olfactory (and gustatory) deficits may occur in dystonia. Finally, we describe the present findings on altered chemical senses in dystonia and discuss directions of research on olfactory dysfunction as a marker in dystonia.

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Novel hyperkinetic dystonia-like manifestation and neurological disease course of Swedish Gaucher patients

Cited by 21 publications

References 162 publications

The Spectrum of Neurological Manifestations Associated with Gaucher Disease

The Spectrum of Neurological Manifestations Associated with Gaucher Disease

Saccadic Impairments in Patients with the Norrbottnian Form of Gaucher’s Disease Type 3

Olfaction as a Marker for Dystonia: Background, Current State and Directions

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