The present study aimed to characterize clinical and molecular data of a large cohort of subjects with childhood-onset hereditary spastic paraplegias (HSPs). A multicenter historical cohort was ...performed at five centers in Brazil, in which probands and affected relatives' data from consecutive families with childhood-onset HSP (onset < 12 years-old) were reviewed from 2011 to 2020. One hundred and six individuals (83 families) with suspicion of childhood-onset HSP were evaluated, being 68 (50 families) with solved genetic diagnosis, 6 (5 families) with candidate variants in HSP-related genes and 32 (28 families) with unsolved genetic diagnosis. The most common childhood-onset subtype was SPG4, 11/50 (22%) families with solved genetic diagnosis; followed by SPG3A, 8/50 (16%). Missense pathogenic variants in SPAST were found in 54.5% of probands, favoring the association of this type of variant to childhood-onset SPG4. Survival curves to major handicap and cross-sectional Spastic Paraplegia Rating Scale progressions confirmed the slow neurological deterioration in SPG4 and SPG3A. Most common complicating features and twenty variants not previously described in HSP-related genes were reported. These results are fundamental to understand the molecular and clinical epidemiology of childhood-onset HSP, which might help on differential diagnosis, patient care and guiding future collaborative trials for these rare diseases.
Abstract
Background Hereditary or familial spastic paraplegias (SPG) comprise a group of genetically and phenotypically heterogeneous diseases characterized by progressive degeneration of the ...corticospinal tracts. The complicated forms evolve with other various neurological signs and symptoms, including movement disorders and ataxia.
Objective To summarize the clinical descriptions of SPG that manifest with movement disorders or ataxias to assist the clinician in the task of diagnosing these diseases.
Methods We conducted a narrative review of the literature, including case reports, case series, review articles and observational studies published in English until December 2022.
Results Juvenile or early-onset parkinsonism with variable levodopa-responsiveness have been reported, mainly in SPG7 and SPG11. Dystonia can be observed in patients with SPG7, SPG11, SPG22, SPG26, SPG35, SPG48, SPG49, SPG58, SPG64 and SPG76. Tremor is not a frequent finding in patients with SPG, but it is described in different types of SPG, including SPG7, SPG9, SPG11, SPG15, and SPG76. Myoclonus is rarely described in SPG, affecting patients with SPG4, SPG7, SPG35, SPG48, and SPOAN (spastic paraplegia, optic atrophy, and neuropathy). SPG4, SPG6, SPG10, SPG27, SPG30 and SPG31 may rarely present with ataxia with cerebellar atrophy. And autosomal recessive SPG such as SPG7 and SPG11 can also present with ataxia.
Conclusion Patients with SPG may present with different forms of movement disorders such as parkinsonism, dystonia, tremor, myoclonus and ataxia. The specific movement disorder in the clinical manifestation of a patient with SPG may be a clinical clue for the diagnosis.
Absence of part or all the iris is called aniridia. This is a distinct ophthalmological feature observed in a restrict group of genetic diseases. The triad of aniridia, congenital ataxia and ...intellectual disability characterize Gillespie syndrome, a recessive or dominant disease caused by ITPR1 gene mutations. Here, Filho et al present the case of a 23-year-old woman with Gillespie syndrome.
Ophthalmological abnormalities may occur in specific subtypes of hereditary spastic paraplegia (HSP) and in genetic diseases that present with spastic paraplegia mimicking HSP. These ophthalmological ...changes may precede the motor symptoms and include pigmentary retinal degeneration, ophthalmoplegia, optic atrophy, cataracts and nystagmus. Some ophthalmological abnormalities are more prevalent in specific forms of HSP. Considering that the diagnosis of HSP is usually difficult and complex, specific ophthalmological changes may guide the genetic testing. There are other genetic diseases such as autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), X-linked adrenoleukodystrophy and spastic paraplegia, optic atrophy and neuropathy (SPOAN) that may mimic HSP and also may present with specific ophthalmological changes. In this article, we review the main ophthalmological changes observed in patients with HSP and HSP-like disorders.
•Hereditary spastic paraplegia may present with ophthalmological manifestations.•Important ophthalmological change associated with SPG15 is retinal degeneration.•Ptosis and progressive external ophthalmoplegia are clues for the diagnosis of SPG7.
Abstract
BACKGROUND
Gait and balance disturbance are challenging symptoms in advanced Parkinson's disease (PD). Anatomic and clinical data suggest that the fields of Forel may be a potential surgical ...target to treat these symptoms.
OBJECTIVE
To test whether bilateral stimulation centered at the fields of Forel improves levodopa unresponsive freezing of gait (FOG), balance problems, postural instability, and falls in PD.
METHODS
A total of 13 patients with levodopa-unresponsive gait disturbance (Hoehn and Yahr stage ≥3) were included. Patients were evaluated before (on-medication condition) and 1 yr after surgery (on-medication-on-stimulation condition). Motor symptoms and quality of life were assessed with the Unified Parkinson's Disease Rating scale (UPDRS III) and Quality of Life scale (PDQ-39). Clinical and instrumented analyses assessed gait, balance, postural instability, and falls.
RESULTS
Surgery improved balance by 43% (95% confidence interval CI: 21.2-36.4 to 35.2-47.1; P = .0012), reduced FOG by 35% (95% CI: 15.1-20.3 to 8.1-15.3; P = .0021), and the monthly number of falls by 82.2% (95% CI: 2.2-6.9 to −0.2-1.7; P = .0039). Anticipatory postural adjustments, velocity to turn, and postural sway measurements also improved 1 yr after deep brain stimulation (DBS). UPDRS III motor scores were reduced by 27.2% postoperatively (95% CI: 42.6-54.3 to 30.2-40.5; P < .0001). Quality of life improved 27.5% (95% CI: 34.6-48.8 to 22.4-37.9; P = .0100).
CONCLUSION
Our results suggest that DBS of the fields of Forel improved motor symptoms in PD, as well as the FOG, falls, balance, postural instability, and quality of life.
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