Elevated FGF 21 in myotonic dystrophy type 1 and mitochondrial diseases.

INTRODUCTION: Human fibroblast growth factor 21 (FGF21) is a regulator of lipid and glucose metabolism. It is expressed in skeletal muscle and may be a sensitive and specific marker for mitochondrial diseases and other neuromuscular disorders. METHODS: Serum FGF21 levels were determined in 71 human samples. Thirty patients with mitochondrial disease, 16 patients with myotonic dystrophy type 1 (DM1), 5 patients with facioscapulohumeral dystrophy, and 20 healthy controls were enrolled. Results Serum FGF21 levels were significantly elevated in patients with progressive external ophthalmoplegia and DM1 compared with patients with facioscapulohumeral dystrophy, other types of mitochondrial diseases, and controls. In the mitochondrial disorder group, serum FGF21 levels were related to the number of ragged blue fibers. Significant insulin resistance was found in DM1 that might be responsible for FGF21 elevation. Conclusions FGF21 elevation may be associated with certain types of mitochondrial disease, and it is influenced by insulin resistance. Muscle Nerve 55: 564-569, 2017.

External ophthalmoplegia associated with Hashimoto's thyroiditis and recovered on corticosteroid treatment.

Five-year follow-up of a young male patient is presented. Total external ophthalmoplegia developed 1 week after an upper respiratory tract infection. After 3 years of the course, hyperthyreosis and clinical signs of thyroid-associated ophthalmopathy occurred. Hashimoto's thyroiditis and ultrastructural signs of mitochondrial damage of striated muscle were found by histological investigations. The paresis of the external ocular muscles recovered after long-term corticosteroid treatment. On the basis of clinical symptoms and histological results, the authors supposed that an immunological reaction had caused mitochondrial damage in the striated muscles, which also resulted in thyroiditis. This case history points that autoimmune mechanism more frequently might participate in the pathogenesis of chronic external ophthalmoplegia, and the symptoms might precede organ-specific or perhaps systemic autoimmune disorders.

Bilateral effects of unilateral thalamic deep brain stimulation: a case report.

A recent study has proved that unilateral deep brain stimulation (DBS) of the subthalamic nucleus has bilateral effects. However, it is still unclear whether unilateral ventral intermediate thalamic nucleus (Vim) DBS exerts exclusively contralateral or bilateral effects on tremor. Previous studies demonstrated a clinically irrelevant improvement on the nontarget side after thalamic stimulator implantation, which was considered to be solely the result of mechanical effects. We report here the case of a 55-year-old woman in whom unilateral thalamic DBS can stop the disabling postural-kinetic tremor in both hands. Simultaneous surface electromyography (sEMG), accelerometry, and video recordings were obtained to evaluate the underlying mechanism. After the right Vim DBS was turned off, moderate rest tremor appeared in both hands accompanied by bilateral bursts on sEMG. Because right hand tremor cannot simply reflect the mechanical overflow of the left side, the bilateral improvement caused by right Vim DBS is probably due to an active tremor reduction in this particular case.

Asymmetric calf hypertrophy of neurogenic origin.

A 47-year-old male presented with painful swelling of the right calf. His medical history was negative, except for a herniation of disc LIV-V 5 years before. Physical examination revealed unilateral calf hypertrophy with moderate weakness of plantarflexion, mild paresis of dorsiflexion. Electromyography showed a peripheral neurogenic lesion in the right anterior tibial muscle, but normal findings were obtained from the unaffected quadriceps muscle. Histological examination of the right gastrocnemic muscle showed neurogenic changes with typical targetoid fibers, but no pathological changes were present in the quadriceps muscle. Chronic asymmetric spinal muscular atrophy is an infrequent neuromuscular disease and because of asymmetric appearance, it might be difficult to distinguish from other, acquired neurogenic muscle diseases such as radiculopathy caused by intervertebral disc herniation. Our case confirms that muscular hypertrophy can follow partial denervation in humans.

Neurosurgical treatment of tremor in mitochondrial encephalopathy.

A 53-year-old woman underwent several ischemic stroke-like episodes and later developed incomplete, bilateral ophthalmoplegia, left vision deterioration, and bilateral tremor. The clinical course, laboratory data, and muscle histology led to a diagnosis of mitochondrial encephalomyopathy. No other etiology could be identified in the background of her disabling bilateral postural-kinetic tremor. As this tremor did not respond to pharmacological therapy, left thalamotomy and subsequently right thalamic deep brain stimulator (DBS) implantation were performed, which resulted in an excellent clinical outcome. The Fahn-Tolosa-Marin Tremor Rating Scale improved from 110 to 11 points. This case suggests that the rare tremor caused by mitochondrial encephalopathy may be treated long-term with either thalamotomy or thalamic DBS implantation.

[Myopathy associated with respiratory insufficiency: diagnostic difficulties in adult-onset Pompe disease]. / Légzészavarral járó myopathia: diagnosztikai nehézségek egy felnottkori Pompe-eset kapcsán.

INTRODUCTION: Adult-onset acid maltase deficiency myopathy is a rare lysosomal storage disease with an autosomal recessive pattern of inheritance. The disease can be manifested with respiratory insufficiency and fatigue. METHODS: A case of a 45-year-old male patient is presented, and difficulty in diagnosis is discussed. RESULTS: The patient had been repeatedly examined because of hypersomnia, dyspnea and fatigue for a full year before a neurological consultation was requested. Artificial ventilation resulted in a dramatic improvement of his symptoms. Neurological examination revealed myopathy. Electrophysiological myotonia and glycogen storage in muscle biopsy specimen suggested acid maltase deficiency. The diagnosis was established by genetic testing detecting the previously described homozygous c.-45T > G mutation in the alpha-glucosidase gene. DISCUSSION: Rare hereditary neurological diseases can be also suspected as cause of chronic unexplained respiratory insufficiency resulted in hypersomnia and fatigue due to hypercapnia and myopathy. A proper diagnosis can contribute to early diagnosis and introduction of enzyme replacement therapy may reduce or stop clinical progression. Genetic diagnosis can also provide a possibility for prenatal testing.

Distal myopathy with rimmed vacuoles and cerebellar atrophy.

Distal myopathies constitute a clinically and pathologically heterogeneous group of genetically determined neuromuscular disorders, where the distal muscles of the upper or lower limbs are affected. The disease of a 41-year-old male patient started with gait disturbances, when he was 25. The progression was slow, but after 16 years he became seriously disabled. Neurological examination showed moderate to severe weakness in distal muscles of all extremities, marked cerebellar sign and steppage gait. Muscle biopsy resulted in myopathic changes with rimmed vacuoles. Brain MRI scan showed cerebellar atrophy. This case demonstrates a rare association of distal myopathy and cerebellar atrophy.

Maternally inherited deafness and unusual phenotypic manifestations associated with A3243G mitochondrial DNA mutation.

The mitochondrial DNA A3243G transition is a fairly common mutation which often associates with a MELAS (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) phenotype, however, a broad variety in the associated clinical picture has also been described. The patient reported here developed a generalized seizure at age 12, which was followed by bilateral hearing loss and occasional fatigue. The maternal inheritance pattern of hearing loss pointed to a possible mitochondrial origin, which was confirmed by molecular analysis of the mitochondrial DNA, revealing a heteroplasmic A3243G transition. Interestingly, muscle biopsy showed ragged-red fibers in the proband, which is unusual in the deafness-associated forms of this mitochondrial disorder. In addition to hearing impairment in four generations of the family, fatal cerebral embolization in the mother and fatal heart attack in the maternal grandmother (both at age 33) also occurred. On the contrary, diabetes, which usually accompanies the hearing loss variant, was specifically absent in all generations. The unusual manifestations associated with this mutation somewhat differentiate this family from the already known variants.

[Diagnosis and therapy of myotonic dystrophy in our practice of neuromuscular care]. / Neuromuscularis gondozásunkban észlelt dystrophia myotonicában szenvedó betegek ismertetése.

INTRODUCTION: Myotonic dystrophy is the most frequent, autosomal dominantly inherited muscular dystrophy. The typical neurological picture (facial myopathy, myotonia, muscle atrophy) may be associated with cardial, endocrine and ocular symptoms. METHODS: The diagnosis is based on electromyography, muscle biopsy and genetical tests. Muscle histology is characterized by high frequency of central nuclei. Genetical tests detect CTG repeat expansion of the involved gene. AIMS: Authors summarize 9 cases found in the Neurology Clinic of Pecs University in the last three years. RESULTS: The prevalence is lower than expected, therefore some cases might be unrecognized. After recognizing the typical clinical picture, electrophysiological, muscle biopsy, brain MRI, psychologic and molecular genetic studies were performed. Six patients belonged to 3 families and 3 sporadic cases were found. In all except one patient mild neurocognitive deficit was detected. Three patients had cataract and cardiac involvement. CONCLUSIONS: The authors emphasize that in cases of cardial, endocrine and central nervous system involvement myotonic dystrophy must be considered and detailed examinations are necessary for early detection of the specific organ manifestations.

[Early onset dementias: three cases]. / Fiatalkori dementiák--Három beteg kórtörténetének ismertetése.

INTRODUCTION: Dementia is a decline of intellectual abilities. The etiology of dementia syndrome is diverse. The authors describe three patients with early-onset dementia. CASE REPORTS: The first patient was a 44 years old male with mild gait, body ataxia, memory loss, slowness and apathy Investigations proved AIDS dementia syndrome. In the second case of a 37 years old female patient, herpes simplex encephalitis was suspected due to sudden onset of speech arrest and to brain MRI and CSF findings. Her symptoms improved during antiviral treatment but later progressive dementia developed. CSF serological tests proved the presence of neurolues-dementia paralytica. The third patient was a 38-years-old female. Neurological examination was performed because of progressive memory loss, changed behaviour and impaired attention. Neuropsychological test showed severe dementia. Metachromatic leukodystrophy was proven by decreased arylsulfatase activity. CONCLUSIONS: It is not easy to recognize the early symptoms of dementia. In these cases, besides detailed history, neurological examination and neuropsychological tests, brain MRI and cerebral spinal fluid serological tests were indispensable for a correct diagnosis, especially in the young patients.