Hajnalka Merkli

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.

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.

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.

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

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.

Acquired neuromyotonia precipitated by thyroid surgery and associated with antiacetylcholine receptor antibodies.

Case Report The thyroid gland of a 62-year-old man was subtotally removed because of nodosal enlargement. Hyperthyroidosis was indicated by elevated free triiodothyromine, free thyroxine and decreased thyroidstimulating hormone levels. Histology did not show any inflammation or tumor tissue, and he has been successfully treated with L-thyroxine. Two weeks after surgery, he realized that he could not relax his grip, and had generalized muscle stiffness. On neurological examination, signs of clinical pseudomyotonia with delayed relaxation were observed without any indication of neuropathy, myopathy or involvement of the central nervous system. No clinical symptoms and signs of MG were observed. Simultaneous concentric needle electromyography on superficial digital flexor, deltoid and abductor pollicis brevis muscles showed continuous spontaneous motor unit activity at rest with reDear Sir, Receptors and ion channels of the neuromuscular junction are targets of several acquired immune-mediated diseases. Antibodies generated against acetylcholine receptors (AchR) result in myasthenia gravis (MG), while antivoltage-gated calcium channels are pathogenic in Lambert-Eaton myasthenic syndrome [1] . Since the description of Isaacs’ syndrome in 1961, several phenotypic variants of acquired peripheral nerve hyperexcitability syndromes have been described [2] . In neuromyotonia, failure to relax voluntary muscle contraction (‘pseudomyotonia’) occurs together with muscle twitching or cramps. Muscle stiffness, increased sweating and hypertrophic calf muscles can be detected in some patients [2] . The association with other autoimmune diseases, especially MG, and the paraneoplastic origin in some cases, e.g. presence of thymoma, suggests an autoimmune origin. Indeed, plasma exchange alleviates the symptoms and the IgG of patients can transfer the disease. Antibodies against voltage-gated potassium channels (VGKC) can be detected in the peripheral blood of the majority of patients [3–5] . Interestingly, antibodies generated against Received: January 25, 2006 Accepted: March 24, 2006 Published online: June 14, 2006

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. Hashimotos 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.

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.