Trends in traumatic spinal cord injuries in Estonia from 1997 to 2018.

OBJECTIVE: To analyze time trends in incidence, causes and risk factors for traumatic spinal cord injuries (TSCI) in Estonia between 1997-2007 and 2008-2018. DESIGN: Retrospective, population-based cohort study. SETTING: Specialized trauma centres in Estonia. PARTICIPANTS: Medical records of patients with TSCI from 1997 to 2018. INTERVENTION: None. OUTCOME MEASURES: Demographical data, crude and age- and sex-adjusted incidence rates, causes of TSCI, level and extent of injury, associated injuries. RESULTS: A total of 940 new patients with TSCI were identified for the period of 1997-2018. The average annual incidence rate (standardized to the Estonian population by age and sex in 2011) decreased significantly from 37.8 (95% confidence interval (CI) 34.6-41.1) in the first period (1997-2008) to 28.2 per million population (95% CI 25.3-31.0) during the second period (2008-2018) (incidence rate ratio 0.74 (95% CI 0.65-0.85), P < 0.0001). The decrease in incidence was most significant among young men. The mean age at injury increased from 38.7 (±16.7) years to 46.6 (±19.9) years, P < 0.0001. Falls were the leading cause of injury during both periods followed by traffic accidents and sports injuries. Still, traffic accidents as a cause of TSCI decreased significantly (from 30.5% to 20.6%, P = 0.001) and falls increased (from 39.9% to 59.5%, P < 0.0001) during the second period. Alcohol consumption prior to injury also decreased significantly from 66.0% to 55.1% (P = 0.006). CONCLUSION: Estonia has become closer to other European countries regarding TSCI during the last decade; TSCI incidence has significantly decreased, the mean age at injury and the percentage of falls have increased.

Subacute administration of both methcathinone and manganese causes basal ganglia damage in mice resembling that in methcathinone abusers.

An irreversible extrapyramidal syndrome occurs in man after intravenous abuse of "homemade" methcathinone (ephedrone, Mcat) that is contaminated with manganese (Mn) and is accompanied by altered basal ganglia function. Both Mcat and Mn can cause alterations in nigrostriatal function but it remains unknown whether the effects of the 'homemade' drug seen in man are due to Mcat or to Mn or to a combination of both. To determine how toxicity occurs, we have investigated the effects of 4-week intraperitoneal administration of Mn (30 mg/kg t.i.d) and Mcat (100 mg/kg t.i.d.) given alone, on the nigrostriatal function in male C57BL6 mice. The effects were compared to those of the 'homemade' mixture which contained about 7 mg/kg of Mn and 100 mg/kg of Mcat. Motor function, nigral dopaminergic cell number and markers of pre- and postsynaptic dopaminergic neuronal integrity including SPECT analysis were assessed. All three treatments had similar effects on motor behavior and neuronal markers. All decreased motor activity and induced tyrosine hydroxylase positive cell loss in the substantia nigra. All reduced 123I-epidepride binding to D2 receptors in the striatum. Vesicular monoamine transporter 2 (VMAT2) binding was not altered by any drug treatment. However, Mcat treatment alone decreased levels of the dopamine transporter (DAT) and Mn alone reduced GAD immunoreactivity in the striatum. These data suggest that both Mcat and Mn alone could contribute to the neuronal damage caused by the 'homemade' mixture but that both produce additional changes that contribute to the extrapyramidal syndrome seen in man.

Acute effects of methcathinone and manganese in mice: A dose response study.

An intravenously injectable illicit drug made by mixing pseudoephedrine, potassium permanganate, vinegar and water, yielding methcathinone (Mcat) and manganese (Mn), induces an extrapyramidal syndrome with parkinsonism, dystonia, gait and balance disorders similar to manganism. Although the cause of the syndrome is largely attributed to Mn, the interaction of the drug's individual components is not known and the role of Mcat is possibly underestimated. Aim of the present study was to analyze dose-dependent behavioral effects of the mixture and its two main active components Mcat and Mn in an acute setting and determine the lethal doses of each substance. Three groups of C57BL/6 mice were injected intraperitoneally with (1) the drug mixture containing 10, 25, 50, 100 or 150 mg of Mcat and respectively 1.6, 3.8, 6.9, 17.1 and 22.6 mg of Mn per kilogram of body weight; (2) 10, 25, 50, 100, 150, 200 or 300 mg of racemic Mcat/kg of body weight; (3) MnCl2 10, 25 or 50 mg/kg of body weight. Locomotor activity of the animals, various signs and time of death were recorded. Lower doses (10 and 25 mg/kg) of Mcat had a clear motor activity stimulating effect and this was clearly dose-dependent. High doses of Mcat produced epileptic seizures in 74% of the animals and became lethal with the highest doses. Similarly, the mixture had a clear dose-dependent stimulating effect and the higher doses became lethal. The LD50 of the pseudoephedrine mixture was 110.2 mg of Mcat/kg and for pure Mcat 201.7 mg/kg. Mn did not prove to be lethal in doses up to 50 mg/kg, but had a strong dose dependent inhibitory effect on the animals' behavior. Our data reveal that both Mn and Mcat have a significant role in the toxicity of the mixture.

Increased striatal VMAT2 binding in mice after chronic administration of methcathinone and manganese.

Intravenous use of a psychostimulant drug containing methcathinone (ephedrone) and manganese causes an irreversible extrapyramidal syndrome in drug abusers. We aimed to reproduce the syndrome in mice to evaluate dopaminergic damage. C57/B6 mice were intraperitoneally injected once a day with the study drug or saline for a period of 27 weeks. Motor activity was recorded in an automated motility-box. After 13 and 27 weeks of treatment, ex vivo digital autoradiography was performed using [11C]dihydrotetrabenazine ([11C]DTBZ). After 27 weeks of treatment [11C]DTBZ autoradiography demonstrated a significant increase in the striatum-to-cerebellum binding ratio compared with saline treated controls. At the same time point, there was no evident change in motor activity. Increased [11C]DTBZ binding may indicate vesicular monoamine transporter type 2 (VMAT2) function is altered. The lack of extrapyramidal symptoms in animals could be attributed to low dosing regimen or high metabolic rate.

Psychostimulants and movement disorders.

Psychostimulants are a diverse group of substances with their main psychomotor effects resembling those of amphetamine, methamphetamine, cocaine, or cathinone. Due to their potential as drugs of abuse, recreational use of most of these substances is illegal since 1971 Convention on Psychotropic Substances. In recent years, new psychoactive substances have emerged mainly as synthetic cathinones with new molecules frequently complementing the list. Psychostimulant related movement disorders are a known entity often seen in emergency rooms around the world. These admissions are becoming more frequent as are fatalities associated with drug abuse. Still the legal constraints of the novel synthetic molecules are bypassed. At the same time, chronic and permanent movement disorders are much less frequently encountered. These disorders frequently manifest as a combination of movement disorders. The more common symptoms include agitation, tremor, hyperkinetic and stereotypical movements, cognitive impairment, and also hyperthermia and cardiovascular dysfunction. The pathophysiological mechanisms behind the clinical manifestations have been researched for decades. The common denominator is the monoaminergic signaling. Dopamine has received the most attention but further research has demonstrated involvement of other pathways. Common mechanisms linking psychostimulant use and several movement disorders exist.

Pharyngoesophageal diverticulum perforation 18 years after anterior cervical fixation.

Anterior cervical spinal surgery can lead to various complications. We hereby present a case of two rare complications combined-pharyngo-oesophageal diverticulum and its perforation after cervical plate dislodgement. A 53-year old male patient presented with progressive dysphagia 18 years after anterior cervical spinal fusion with tricortical bone graft and custom-made plate at the C6/7 level. Oesophagography revealed a pharyngo-oesophageal diverticulum in front of the cervical plate. It was confirmed by subsequent oesophagoscopy, which also demonstrated a 3-cm longitudinal defect at the posterior wall of the diverticulum. During surgical exploration of the patient's neck, the plate was removed, the diverticulum was completely mobilized and excised, the oesophageal wall manually sutured and a cricopharyngeal myotomy performed. An oesophageal suture line failure was suspected postoperatively, but was not confirmed during reoperation. A year later, the patient has no dysphagia or any other symptoms.