Human eye fixation is steadily interrupted by small, physiological or abnormal, eye movements. Square-wave jerks (SWJ) are the most common saccadic intrusion which can be readily seen at the bedside ...and also quantified using oculographic techniques. Various neurological, neuropsychiatric and psychiatric disorders display abnormal fixational eye movement patterns characterized by frequent SWJ. For the clinician, SWJ are particularly important because they can be readily observed at the bedside. Here, we will discuss the pathological conditions that present with SWJ and explore the expanding body of literature suggesting that SWJ may serve as a potential indicator for various clinical conditions.
Previous epidemiological evidence has established the co-occurrence of malignant melanoma (MM) and Parkinson's disease (PD). Shared molecular mechanisms have been proposed to be implicated in this ...relationship. The aim of the present study was to assess the prevalence of MM in patients with sporadic and genetic types of PD, as well as in asymptomatic carriers of PD-related genes.
Data regarding past medical history and concomitant disease of 1416 patients with PD (including 20 participants with prodromal disease who phenoconverted to PD), 275 healthy controls (HCs) and 670 asymptomatic carriers of PD-related genes were obtained from the database of the Parkinson's Progression Markers Initiative (PPMI). Focus was placed on information about a medical record of MM. We also retrieved data regarding the genetic status of selected PPMI participants with a positive MM history.
In total, 46 patients with PD reported a positive MM history. Concerning the genetic forms of PD, nine of these PD patients (2.47%) carried a Leucine Rich Repeat Kinase 2 (LRRK2) gene mutation (mainly the G2019S), while eight (4.49%) harbored a Glucocerebrosidase (GBA) gene mutation (mainly the N370S). No alpha-synuclein (SNCA) gene mutation was identified in patients with an MM history. The remaining 29 PD patients (3.5%) were genetically undetermined. In total, 18 asymptomatic carriers of PD-related genes had a positive medical history for MM: among them, 10 carried an LRRK2 gene mutation (2.69%) and 10 a GBA gene mutation (3.51%) (2 were dual carriers). MM history was identified for seven HCs (2.5%).
We replicated the previously reported association between genetically undetermined PD (GU-PD) and MM. A correlation of LRRK2 mutations with the development of MM could not be verified in either symptomatic PD patients or asymptomatic carriers, implicating distinct pathogenetic mechanisms as compared to GU-PD. Importantly, despite the limited literature evidence on Gaucher disease, this study highlights for the first time the relatively high prevalence of MM among asymptomatic and symptomatic PD GBA mutation carriers, with potential clinical implications.
Aims of the present article are:
) assessing vestibular contribution to spatial navigation,
) exploring how age, global positioning systems (GPS) use, and vestibular navigation contribute to ...subjective sense of direction (SOD),
) evaluating vestibular navigation in patients with lesions of the vestibular-cerebellum (patients with downbeat nystagmus, DBN) that could inform on the signals carried by vestibulo-cerebellar-cortical pathways. We applied two navigation tasks on a rotating chair in the dark: return-to-start (RTS), where subjects drive the chair back to the origin after discrete angular displacement stimuli (path reversal), and complete-the-circle (CTC) where subjects drive the chair on, all the way round to origin (path completion). We examined 24 normal controls (20-83 yr), five patients with DBN (62-77 yr) and, as proof of principle, two patients with early dementia (84 and 76 yr). We found a relationship between SOD, assessed by Santa Barbara Sense of Direction Scale, and subject's age (positive), GPS use (negative), and CTC-vestibular-navigation-task (positive). Age-related decline in vestibular navigation was observed with the RTS task but not with the complex CTC task. Vestibular navigation was normal in patients with vestibulo-cerebellar dysfunction but abnormal, particularly CTC, in the demented patients. We conclude that vestibular navigation skills contribute to the build-up of our SOD. Unexpectedly, perceived SOD in the elderly is not inferior, possibly explained by increased GPS use by the young. Preserved vestibular navigation in cerebellar patients suggests that ascending vestibular-cerebellar projections carry velocity (not position) signals. The abnormalities in the cognitively impaired patients suggest that their vestibulo-spatial navigation is disrupted.
Our subjective sense-of-direction is influenced by how good we are at spatial navigation using vestibular cues. Global positioning systems (GPS) may inhibit sense of direction. Increased use of GPS by the young may explain why the elderly's sense of direction is not worse than the young's. Patients with vestibulo-cerebellar dysfunction (downbeat nystagmus syndrome) display normal vestibular navigation, suggesting that ascending vestibulo-cerebellar-cortical pathways carry velocity rather than position signals. Pilot data indicate that dementia disrupts vestibular navigation.
Monocular torsional eye oscillations are a rare form of disconjugate nystagmus and the underlying pathophysiology is not well understood. Here, we present and discuss a case with disabling torsional ...oscillopsia in one eye only. The patient exhibited (i) spontaneous pendular torsional nystagmus of the left eye and (ii) rhythmic involuntary movements of the soft palate and uvula, consistent with the syndrome of oculopalatal tremor with monocular nystagmus. Brain MRI revealed an infarct of the left dentate nucleus in the cerebellum and, more caudally, a secondary hypertrophic degeneration of the right inferior olivary nucleus. To account for the presence of torsional nystagmus on the eye contralateral to the side of inferior olivary hypertrophy and ipsilateral to the lesioned dentate nucleus, we discuss the hypothesis of a (inferior olivary nucleus-mediated) malfunctioning adaptation of the anterior canal vestibulo-ocular reflex.
ITPR1 gene encodes inositol 1,4,5-trisphosphate-receptor-type 1, a Ca2+ channel highly expressed in cerebellar Purkinje cells. ITPR1 gene variants, through a loss-of-function mechanism, have been ...found to be related with the manifestation of spinocerebellar ataxia (SCA) 15, an adult-onset slow progressive cerebellar ataxia, SCA 29, a rare non-progressive congenital cerebellar ataxia and Gillepsie syndrome (SCA 29 phenotype plus aniridia). They share an heterogeneity of additional phenotypic features while no genotype-phenotype correlation has ever been found.
Here we report the case of a boy with cerebellar ataxia who came to our clinic due to his cervical dystonia in the form of retrocollis. He presented an early-onset, non-progressive cerebellar ataxia, with cognitive impairment and delayed motor milestones. Whole exome sequencing (WES) revealed an heterozygous nucleotide variation, c.829A > C (p.Ser277Arg) in ITPR1 gene (NM_001168272.1), a de novo ITPR1 variant, as his parents came up with negative genetic testing. Due to his clinical presentation and genetic result, we came up with the diagnosis of SCA 29.
We described cervical dystonia as a phenotypic feature of ITPR1 related SCA 29, found in a new de novo ITPR1-variant.
BACKGROUNDITPR1 gene encodes inositol 1,4,5-trisphosphate-receptor-type 1, a Ca2+ channel highly expressed in cerebellar Purkinje cells. ITPR1 gene variants, through a loss-of-function mechanism, ...have been found to be related with the manifestation of spinocerebellar ataxia (SCA) 15, an adult-onset slow progressive cerebellar ataxia, SCA 29, a rare non-progressive congenital cerebellar ataxia and Gillepsie syndrome (SCA 29 phenotype plus aniridia). They share an heterogeneity of additional phenotypic features while no genotype-phenotype correlation has ever been found. CASE REPORTHere we report the case of a boy with cerebellar ataxia who came to our clinic due to his cervical dystonia in the form of retrocollis. He presented an early-onset, non-progressive cerebellar ataxia, with cognitive impairment and delayed motor milestones. Whole exome sequencing (WES) revealed an heterozygous nucleotide variation, c.829A > C (p.Ser277Arg) in ITPR1 gene (NM_001168272.1), a de novo ITPR1 variant, as his parents came up with negative genetic testing. Due to his clinical presentation and genetic result, we came up with the diagnosis of SCA 29. CONCLUSIONWe described cervical dystonia as a phenotypic feature of ITPR1 related SCA 29, found in a new de novo ITPR1-variant.
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