Apraxia of speech and cerebellar mutism syndrome: a case study

Background Cerebellar mutism syndrome (CMS) or posterior fossa syndrome (PFS) consists of a constellation of neuropsychiatric, neuropsychological and neurogenic speech and language deficits. It is most commonly observed in children after posterior fossa tumor surgery. The most prominent feature of CMS is mutism, which generally starts after a few days after the operation, has a limited duration and is typically followed by motor speech deficits. However, the core speech disorder subserving CMS is still unclear. Case presentation This study investigates the speech and language symptoms following posterior fossa medulloblastoma surgery in a 12-year-old right-handed boy. An extensive battery of formal speech (DIAS = Diagnostic Instrument Apraxia of Speech) and language tests were administered during a follow-up of 6 weeks after surgery. Although the neurological and neuropsychological (affective, cognitive) symptoms of this patient are consistent with Schmahmann’s syndrome, the speech and language symptoms were markedly different from what is typically described in the literature. In-depth analyses of speech production revealed features consistent with a diagnosis of apraxia of speech (AoS) while ataxic dysarthria was completely absent. In addition, language assessments showed genuine aphasic deficits as reflected by distorted language production and perception, wordfinding difficulties, grammatical disturbances and verbal fluency deficits. Conclusion To the best of our knowledge this case might be the first example that clearly demonstrates that a higher level motor planning disorder (apraxia) may be the origin of disrupted speech in CMS. In addition, identification of non-motor linguistic disturbances during follow-up add to the view that the cerebellum not only plays a crucial role in the planning and execution of speech but also in linguistic processing. Whether the cerebellum has a direct or indirect role in motor speech planning needs to be further investigated

Endocrine and Growth Abnormalities in 4H Leukodystrophy Caused by Variants in POLR3A, POLR3B, and POLR1C.

CONTEXT: 4H or POLR3-related leukodystrophy is an autosomal recessive disorder typically characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism, caused by biallelic pathogenic variants in POLR3A, POLR3B, POLR1C, and POLR3K. The endocrine and growth abnormalities associated with this disorder have not been thoroughly investigated to date. OBJECTIVE: To systematically characterize endocrine abnormalities of patients with 4H leukodystrophy. DESIGN: An international cross-sectional study was performed on 150 patients with genetically confirmed 4H leukodystrophy between 2015 and 2016. Endocrine and growth abnormalities were evaluated, and neurological and other non-neurological features were reviewed. Potential genotype/phenotype associations were also investigated. SETTING: This was a multicenter retrospective study using information collected from 3 predominant centers. PATIENTS: A total of 150 patients with 4H leukodystrophy and pathogenic variants in POLR3A, POLR3B, or POLR1C were included. MAIN OUTCOME MEASURES: Variables used to evaluate endocrine and growth abnormalities included pubertal history, hormone levels (estradiol, testosterone, stimulated LH and FSH, stimulated GH, IGF-I, prolactin, ACTH, cortisol, TSH, and T4), and height and head circumference charts. RESULTS: The most common endocrine abnormalities were delayed puberty (57/74; 77% overall, 64% in males, 89% in females) and short stature (57/93; 61%), when evaluated according to physician assessment. Abnormal thyroid function was reported in 22% (13/59) of patients. CONCLUSIONS: Our results confirm pubertal abnormalities and short stature are the most common endocrine features seen in 4H leukodystrophy. However, we noted that endocrine abnormalities are typically underinvestigated in this patient population. A prospective study is required to formulate evidence-based recommendations for management of the endocrine manifestations of this disorder

Retrograde transport of bisbenzimide and propidium iodide through axons to their parent cell bodies

Two fluorescent substances bisbenzimide (Bb), which fluoresces yellow-green and propidium iodide (PI), which fluoresces orange were found to be transported retrogradely through axons to their parent cell bodies in rat and cat. Bb gives a very strong and long lasting fluorescent retrograde neuronal labeling and is very effectively transported over long distances both in rat and cat. Bb and PI also label glial nuclei around retrogradely labeled neurons. Bb in addition labels glial nuclei along axons through which it is transported. Bb and PI can be transported retrogradely through two divergent collaterals to one and the same cell

Posterior fossa syndrome in a patient with an ornithine transcarbamylase deficiency

The posterior fossa syndrome (PFS) is a well-known clinical entity and mainly occurs in children. Ornithine transcarbamylase deficiency (OTC) is the most common urea cycle disorder, which occurs in an estimated 1 per 50.000 live births in Japan. Symptoms are mostly due to hyperammonemia and include nausea, vomiting, lethargia and even convulsions and coma. Common neurological symptoms at presentation of a hyperammonemia are a decreased level of consciousness, abnormal motor function or seizures. In this case we describe a girl with late onset OCT deficiency presenting with transient mutism and subsequent dysarthria, ataxia and behavioural changes. This is an exceptional report of a not yet described neurologic syndrome in OTC. Synopsis: Neurologic symptoms in ornithine transcarbamylase deficiency do not only occur during an episode of hyperammonemia and may present as a transient neurologic symptoms compatible with the posterior fossa syndrome