α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid Receptor Plasticity Sustains Severe, Fatal Status Epilepticus.

OBJECTIVE: Generalized convulsive status epilepticus is associated with high mortality. We tested whether α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor plasticity plays a role in sustaining seizures, seizure generalization, and mortality observed during focal onset status epilepticus. We also determined whether modified AMPA receptors generated during status epilepticus could be targeted with a drug. METHODS: Electrically induced status epilepticus was characterized by electroencephalogram and behavior in GluA1 knockout mice and in transgenic mice with selective knockdown of the GluA1 subunit in hippocampal principal neurons. Excitatory and inhibitory synaptic transmission in CA1 neurons was studied using patch clamp electrophysiology. The dose response of N,N,H,-trimethyl-5-([tricyclo(3.3.1.13,7)dec-1-ylmethyl]amino)-1-pentanaminiumbromide hydrobromide (IEM-1460), a calcium-permeable AMPA receptor antagonist, was determined. RESULTS: Global removal of the GluA1 subunit did not affect seizure susceptibility; however, it reduced susceptibility to status epilepticus. GluA1 subunit knockout also reduced mortality, severity, and duration of status epilepticus. Absence of the GluA1 subunit prevented enhancement of glutamatergic synaptic transmission associated with status epilepticus; however, γ-aminobutyric acidergic synaptic inhibition was compromised. Selective removal of the GluA1 subunit from hippocampal principal neurons also reduced mortality, severity, and duration of status epilepticus. IEM-1460 rapidly terminated status epilepticus in a dose-dependent manner. INTERPRETATION: AMPA receptor plasticity mediated by the GluA1 subunit plays a critical role in sustaining and amplifying seizure activity and contributes to mortality. Calcium-permeable AMPA receptors modified during status epilepticus can be inhibited to terminate status epilepticus. ANN NEUROL 2020;87:84-96.

Parallel pathways of seizure generalization.

Generalized convulsive status epilepticus is a life-threatening emergency, because recurrent convulsions can cause death or injury. A common form of generalized convulsive status epilepticus is of focal onset. The neuronal circuits activated during seizure spread from the hippocampus, a frequent site of seizure origin, to the bilateral motor cortex, which mediates convulsive seizures, have not been delineated. Status epilepticus was initiated by electrical stimulation of the hippocampus. Neurons transiently activated during seizures were labelled with tdTomato and then imaged following brain slice clearing. Hippocampus was active throughout the episode of status epilepticus. Neuronal activation was observed in hippocampus parahippocampal structures: subiculum, entorhinal cortex and perirhinal cortex, septum, and olfactory system in the initial phase status epilepticus. The tdTomato-labelled neurons occupied larger volumes of the brain as seizures progressed and at the peak of status epilepticus, motor and somatosensory cortex, retrosplenial cortex, and insular cortex also contained tdTomato-labelled neurons. In addition, motor thalamic nuclei such as anterior and ventromedial, midline, reticular, and posterior thalamic nuclei were also activated. Furthermore, circuits proposed to be crucial for systems consolidation of memory: entorhinal cortex, retrosplenial cortex, cingulate gyrus, midline thalamic nuclei and prefrontal cortex were intensely active during periods of generalized tonic-clonic seizures. As the episode of status epilepticus waned, smaller volume of brain was activated. These studies suggested that seizure spread could have occurred via canonical thalamocortical pathway and many cortical structures involved in memory consolidation. These studies may help explain retrograde amnesia following seizures.

Electroencephalography and behavior patterns during experimental status epilepticus.

OBJECTIVE: To characterize the evolution of behavioral and electrographic seizures in an experimental electrical stimulation-based model of status epilepticus (SE) in C57Bl/6 mice, and to relate SE to various outcomes, including death and epileptogenesis. METHODS: SE was induced by continuous hippocampal stimulation and was evaluated by review of electroencephalographic recordings, spectral display, and behavior. RESULTS: Seizures were initially locked to the electrical trains but later became independent of them. Following the end of stimulation, autonomous seizures continued for >5 minutes in 85% of the animals. There was ongoing 2-3-Hz rhythmic, high-amplitude, slow spike-wave discharges (HASDs) associated with purposeless, repetitive, continuously circling and exploratory behavior. There were high-amplitude fast discharges (HAFDs) associated with worsening of behavioral seizures that were interspersed with the ongoing HASDs. Death during SE occurred in 23% of the animals, and it was preceded by a stage 5 behavioral seizure. In the waning stage of SE, severe seizures and HAFDs dissipated, HASDs slowed down, and normal behavior was restored in most animals. Epilepsy developed in 33% of the animals monitored after SE. SIGNIFICANCE: The electrical stimulation model of SE can be used to study mechanisms of SE and its adverse consequences, including death and epileptogenesis.

[Occupational and non-occupational aspects of carpal tunnel syndrome]. / Zawodowe i pozazawodowe aspekty zespolu kanalu nadgarstka.

Carpal tunnel syndrome is caused by the pressure of the medianus nerve in the carpal canal. This syndrome is characterized by the following symptoms: numbness of the thumb and fingers, hand pain, particularly at night, and handicap of the hand efficiency. The examination of the perception, provocation tests, electromyography, carpal radiography, ultrasonography and magnetic resonance imaging are very helpful in the diagnosis of carpal tunnel syndrome. Pathological changes in flexor's theca are the most frequent causes of the syndrome. It may also occur in patients with lupus erythematosus, tuberculosis, endocrinopathy, rheumatic diseases and during pregnancy. Carpal tunnel syndrome is one of the most common occupational neuropathy. It is associated with the recurrence of carpal movements and observed in seamstresses, butchers, persons testing bar codes in supermarkets and meat packers.

[A case of lung silicosis associated with plasmocytoma: the diagnosis and certification difficulties]. / Przypadek krzemicy pluc wspólistniejacy ze szpiczakiem--trudnosci diagnostyczne i orzecznicze.

Silicosis is a chronic, progressing disease of the respiratory system. The aim of this paper was to describe a case of silicosis coexisting with not typical plasmocytoma. Silicosis was diagnosed in a 62-year old woman, after an 8-year employment as a grinder. The patient has suffered from progressing weakness, fatigue, and dyspnea for 2 years. The increased leucocytosis (18-20,000) and moderate lymphocytosis were found in laboratory tests. The patient was admitted to the hospital in a very serious condition, with fever and progressing insufficiency of the respiratory and circulatory systems. Following computed tomography (CT), tumorous silicosis was diagnosed in the Department of Internal and Occupational Diseases. After three months, the increased level of the whole number of serum proteins (until 90 g/l) was found for the first time together with few places of osteolysis in the x-ray cranium picture. The plasmocytoma infiltrations were found in the post-mortem lung examination. The described case seems to be interesting in view of a possible induction of monoclonal gammopathy by silicosis.

[Occupational health problems in dental practice]. / Zawodowe zagrozenia zdrowotne w gabinetach stomatologicznych.

The overload of the osteoarticular system resulting from standing and stooping position of the body is the main health problem of dentists. This may cause vertebral pain, symptoms of sciatica and foot valgo-planus. Symptoms of carpal tunnel syndrome are induced by repeated carpus movements. Frequent numbness associated with the peripheral nerves changes result from using drills by dentists. Menstruation disturbances observed in dental assistants could be related to the increased levels of mercury in serum and urine. Allergy is also a frequent medical problem, particularly allergy to latex. manifested by contact eczema or allergic urticaria, asthma and shock. There also is an increased risk for infectious diseases through the contact with biological material, mostly saliva and blood.