Health and well-being of maturing adults with classic galactosemia.

Long-term outcomes in classic galactosemia (CG) have been studied previously, but all prior studies have relied on cohorts of patients that were small in number, or heavily skewed toward children and young adults, or both. Here, we extend what is known about the health and well-being of maturing adults with CG by analyzing the results of anonymous custom surveys completed by 92 affected individuals, ages 30-78, and 38 unaffected sibling controls, ages 30-79. The median age for patients was 38.5 years and for controls was 41 years. These study participants hailed from 12 different countries predominantly representing Europe and North America. Participants reported on their general life experiences and outcomes in seven different domains including: speech/voice/language, cognition, motor function, cataracts, bone health, psychosocial well-being, and gastrointestinal health. We also queried women about ovarian function. Our results indicated a prevalence of long-term complications across all outcome domains that aligned with levels previously reported in younger cohorts. Given the sample size and age range of participants in this study, these findings strongly suggest that the adverse developmental outcomes commonly linked to CG are not progressive with age for most patients. We also tested four candidate modifiers for possible association with each of the outcomes followed, including: days of neonatal milk exposure, rigor of dietary galactose restriction in early childhood, current age, and home continent. We observed no associations that reached even nominal significance, except for the following: cataracts with neonatal milk exposure (p = 2.347e-04), cataracts with age (p = 0.018), and bone health with home continent (p = 0.03).

Clinical Reasoning: A Woman With Progressive Painless Sequential Monocular Vision Loss.

A 68-year-old woman with a history of diabetes mellitus type 2, depression, and migraines presented with painless, acute, consecutive vision loss affecting the right eye for 1 week and the left eye for 2 weeks. Neuro-ophthalmic examination was notable for visual acuities of finger-counting peripherally, a central scotoma, anterior uveitis, vitritis, and placoid macular pigmentary changes in each eye (OU). Proprioception was diminished in the bilateral lower extremities. Optical coherence tomography (OCT) revealed hyper-reflectivity and attenuation of the outer retina OU with normal inner retinal architecture and reflectivity. Fluorescein angiography (FA) demonstrated normal filling of the central retinal arteries with patchy choroidal perfusion in the right eye and targetoid punctate foci of leakage in the macula OU. Before the recognition of intraocular inflammation and findings on OCT and FA, the patient was treated for presumed central retinal artery occlusion at an outside hospital. Additional diagnostic testing at our institution revealed an alternate diagnosis. This case highlights a rare presentation of a well-known disease entity and underscores the importance of avoiding diagnostic anchoring in clinical practice.

Identification of neuronal structures and pathways corresponding to clinical functioning in galactosemia.

Classic galactosemia (OMIM# 230400) is an autosomal recessive disorder due to galactose-1-phosphate uridyltransferase deficiency. Newborn screening and prompt treatment with a galactose-free diet prevent the severe consequences of galactosemia, but clinical outcomes remain suboptimal. Five men and five women with classic galactosemia (mean age = 27.2 ± 5.47 years) received comprehensive neurological and neuropsychological evaluations, electroencephalogram (EEG) and magnetic resonance imaging (MRI). MRI data from nine healthy controls (mean age = 30.22 ± 3.52 years) were used for comparison measures. Galactosemia subjects experienced impaired memory, language processing, visual-motor skills, and increased anxiety. Neurological examinations revealed tremor and dysarthria in six subjects. In addition, there was ataxia in three subjects and six subjects had abnormal gait. Mean full scale IQ was 80.4 ± 17.3. EEG evaluations revealed right-sided abnormalities in five subjects and bilateral abnormalities in one subject. Compared to age- and gender-matched controls, subjects with galactosemia had reduced volume in left cerebellum white matter, bilateral putamen, and left superior temporal sulcus. Galactosemia patients also had lower fractional anisotropy and higher radial diffusivity values in the dorsal and ventral language networks compared to the controls. Furthermore, there were significant correlations between neuropsychological test results and the T1 volume and diffusivity scalars. Our findings help to identify anatomic correlates to motor control, learning and memory, and language in subjects with galactosemia. The results from this preliminary assessment may provide insights into the pathophysiology of this inborn error of metabolism.

Percutaneous Transverse Sinus Cannulation for Dural Arteriovenous Fistula Coiling: Operative Video.

This is the case of an 84-year old woman, found to have a symptomatic transverse sinus dural arteriovenous fistula. The transverse sinus was isolated from all venous circulation and its arterial feeders stemmed from the occipital artery, precluding both arterial and venous access for effective obliteration of the fistula. Therefore the patient underwent a combined open surgical/endovascular approach, where the sinus was percutaneously cannulated through a single burr hole, allowing access for effective coiling of the fistula. In this video, we present the rationale, feasibility, and technical implications for this procedure.1.

Repetitive Transcranial Magnetic Stimulation in Spinocerebellar Ataxia: A Pilot Randomized Controlled Trial.

Spinocerebellar ataxia (SCA) is a neurodegenerative disorder caused by dysfunction of the cerebellum and its connected neural networks. There is currently no cure for SCA and symptomatic treatment remains limited. We aimed here to examine the effects of a repetitive transcranial magnetic stimulation (rTMS) targeting the cerebellum on clinical impression, postural control and gait in patients with SCA. In this randomized, double-blinded and sham-controlled study, 20 individuals aged 18-75 years with SCA confirmed by genetic testing completed rTMS or sham intervention comprising 20 sessions of MRI-guided stimulation over the cerebellum. Baseline assessments included the Standard Ataxia Rating Assessment (SARA), the 9-hole peg test of manual dexterity, the Timed Up-and-Go (TUG) test, standing postural control with eyes-open and eyes-closed, and gait. Immediate (within 1-week) and 1-month follow-ups were completed. Intervention compliance was high (19 ± 2 of 20 sessions) and no rTMS-related adverse events were reported. rTMS, compared to sham, was associated with greater percent improvement in SARA total score from baseline to the 1-month follow-up (p = 0.008). Secondary analyses of individual SARA items revealed that rTMS improved performance within the "stance" sub-score only (p = 0.002). This functional change was accompanied by improvement to several objective metrics of postural sway during eyes-open and eyes-closed standing (p < 0.008). rTMS did not influence the 9-hole peg test, TUG, or gait kinematics. A 20-session rTMS intervention is safe and feasible for those with SCA. Additional research is warranted to confirm the observed longer-term benefits of this intervention on standing postural control. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT01975909.

Comprehensive systematic review summary: Treatment of cerebellar motor dysfunction and ataxia: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology.

OBJECTIVE: To systematically review evidence regarding ataxia treatment. METHODS: A comprehensive systematic review was performed according to American Academy of Neurology methodology. CONCLUSIONS: For patients with episodic ataxia type 2, 4-aminopyridine 15 mg/d probably reduces ataxia attack frequency over 3 months (1 Class I study). For patients with ataxia of mixed etiology, riluzole probably improves ataxia signs at 8 weeks (1 Class I study). For patients with Friedreich ataxia or spinocerebellar ataxia (SCA), riluzole probably improves ataxia signs at 12 months (1 Class I study). For patients with SCA type 3, valproic acid 1,200 mg/d possibly improves ataxia at 12 weeks. For patients with spinocerebellar degeneration, thyrotropin-releasing hormone possibly improves some ataxia signs over 10 to 14 days (1 Class II study). For patients with SCA type 3 who are ambulatory, lithium probably does not improve signs of ataxia over 48 weeks (1 Class I study). For patients with Friedreich ataxia, deferiprone possibly worsens ataxia signs over 6 months (1 Class II study). Data are insufficient to support or refute the use of numerous agents. For nonpharmacologic options, in patients with degenerative ataxias, 4-week inpatient rehabilitation probably improves ataxia and function (1 Class I study); transcranial magnetic stimulation possibly improves cerebellar motor signs at 21 days (1 Class II study). For patients with multiple sclerosis-associated ataxia, the addition of pressure splints possibly has no additional benefit compared with neuromuscular rehabilitation alone (1 Class II study). Data are insufficient to support or refute use of stochastic whole-body vibration therapy (1 Class III study).

Cerebellar TMS in treatment of a patient with cerebellar ataxia: evidence from clinical, biomechanics and neurophysiological assessments.

We describe a patient with a probable diagnosis of idiopathic late-onset cerebellar atrophy who shows improvement of limb coordination, speech, and gait following 21 days of transcranial magnetic stimulation (TMS) applied to scalp regions presumably corresponding to the cerebellum. This case study provides, for the first time, a quantitative assessment of gait improvement in response to TMS therapy in ataxia, as well as neurophysiological evidence in support of modification of cerebellar-cortical interaction that may underlie some of the improvements.