Gabapentin and sexual dysfunction: report of two cases

Gabapentin has been used effectively for neuropathic pain with mild side effects. Two cases of gabapentin-induced sexual dysfunction are reported and discussed.     

Gabapentin-induced sexual dysfunction

Sexual dysfunction is a key adverse effect leading to medication noncompliance. Psychotropic drugs associated with sexual dysfunction include antiepileptic drugs, antidepressants, and antipsychotics. Gabapentin, frequently used off-label to treat psychiatric and pain disorders, has previously been reported to cause sexual dysfunction at a minimum total daily dose of 900 mg. This report addresses dose-dependent gabapentin-induced sexual dysfunction reaching total sexual dysfunction (loss of libido, anejaculation, anorgasmia, and impotence) at a total daily dose of only 300 mg.     

Presynaptic NMDA autoreceptors facilitate axon excitability: a new molecular target for the anticonvulsant gabapentin

Gabapentin is a drug with anticonvulsant and analgesic properties causing the reduction of neurotransmitter release. We show that one of the mechanisms implicated in this effect of gabapentin is the reduction of the axon excitability measured as an amplitude change of the presynaptic fibre volley (FV) in the CA1 area of rat hippocampal slices. Interestingly, we found that gabapentin-induced depression of FV is mimicked and occluded by NMDA receptor (NMDA-R) antagonists, indicating that these receptors are located presynaptically and are activated by ambient levels of glutamate. Conversely, NMDA application (20 microM, 10 min) elicits a reversible FV potentiation which is reduced by gabapentin. Both NMDA- and gabapentin-induced FV changes are partially explained by modifications in the firing threshold of individual fibres. Increasing [K(+)](o) does not mimic or occlude (at a concentration of 6.5 mM) the effect of NMDA on FV amplitude, which makes it unlikely that a rise in [K(+)](o) induced by NMDA receptor activation could indirectly participate in the potentiation of the FV. The NMDA-induced FV potentiation is independent of extracellular calcium presence but is completely inhibited in a low-Na(+) solution (50% reduction) or under NMDA channel block (high Mg(2+) or MK 801). These findings suggest that sodium entry through presynaptic NMDA-R channels facilitates axon excitability. The interaction of gabapentin with this newly described mechanism might contribute to its therapeutic benefits.     

Electroencephalographic assessment of coma.

SUMMARY: Altered mental status ranging from confusion to deep unresponsiveness can be described as coma. Electroencephalography is an important tool in assessing comatose patients. Some EEG patterns are seen with lighter stages of coma and have a good prognosis, whereas others are seen in deep, often irreversible coma. These EEG patterns carry a much more grave prognosis. This paper discusses the various EEG features seen in coma, ranging from intermittent rhythmic delta activity to electrocerebral inactivity. A discussion regarding etiology and prognosis is presented after the EEG pattern is described in detail. Special EEG features, such as alpha coma, beta coma, spindle coma, etc., are discussed toward the end.     

Nonconvulsive status epilepticus and coma

Nonconvulsive status epilepticus (NCSE) in a comatose patient cannot be diagnosed without electroencephalography (EEG). In many advanced coma stages, the EEG exhibits continuous or periodic EEG abnormalities, but their causal role in coma remains unclear in many cases. To date there is no consensus on whether to treat NCSE in a comatose patient in order to improve the outcome or to retract from treatment, as these EEG patterns might reflect the end stages of a dying brain. On the basis of EEG, NCSE in comatose patients may be classified as generalized or lateralized. This review aims to summarize the ongoing debate of NCSE and coma and to critically reassess the available literature on coma with epileptiform EEG pattern and its prognostic and therapeutic implications. The authors suggest distinguishing NCSE proper and comatose NCSE, which includes coma with continuous lateralized discharges or generalized epileptiform discharges (coma‐LED, coma‐GED). Although NCSE proper is accompanied by clinical symptoms suggestive of status epilepticus and mild impairment of consciousness, such as in absence status or complex focal status epilepticus, coma‐LED and coma‐GED represent deep coma of various etiology without any clinical motor signs of status epilepticus but with characteristic epileptiform EEG pattern. Hence coma‐LED and coma‐GED can be diagnosed with EEG only. Subtle or stuporous status epilepticus and epilepsia partialis continua–like symptoms in severe acute central nervous system (CNS) disorders represent the borderland in this biologic continuum between NCSE proper and comatose NCSE (coma‐LED/GED). This pragmatic differentiation could act as a starting point to solve terminologic and factual confusion.     

Physiologic and prognostic significance of "alpha coma".

A patient with posthypoxic "alpha coma" is described whose EEGs were recorded before coma, within two hours following the onset of coma and after recovery. The differences observed between the alpha activity during coma and that seen before and after suggest that the alpha activity during coma and the physiologic alpha rhythm are different phenomena. This case, as well as others reported, also suggests that "alpha coma" resolving in the first 24 hours following hypoxia may have a better prognosis than "alpha coma" detected after the first day, and stresses the need for EEG monitoring begun in the immediate period following hypoxia in order to assess accurately the prognostic significance of this EEG pattern in the early stages of postanoxic encephalopathy. The aetiology of "alpha coma" also affects outcome. The survival rate appears higher in patients with respiratory arrest than in those with combined cardiopulmonary arrest.     

"Theta pattern coma" occurring in younger adults

Since our previous report, where "theta pattern coma" was described in 2 elderly patients as an EEG pattern with a grave prognosis, we have had the opportunity to see another 9 affected patients. In this article, 3 men with a mean age of 36 years who died after cardiorespiratory arrest presented a "theta coma pattern." The EEG activity was initially reactive to and attenuated by external stimulation in 2, but prior to death the pattern became arreactive. This article shows that "theta pattern coma" is not an age related phenomenon as previously considered. So far, 11 patients with this type of EEG abnormality have been seen in our department; all have died, and all were over 30 years of age. An expanded definition of "theta pattern coma" is given in the discussion. The pathophysiological mechanisms involved in generation of this abnormality are not known. This abnormality, when seen in the unconscious patient, should be classified as a grade 4 abnormality on the EEG coma scale and should be differentiated from rather diffuse theta activity in coma. The prognostic significance of "theta pattern coma" appears to be similar to that of "alpha pattern coma."     

CNS tryptamine metabolism in hepatic coma

Summary Lumbar CSF indoleacetic acid (IAA) was higher in patients with cirrhosis of the liver than in controls. It was also higher in CSF of patients in coma than in those with hepatic cirrhosis but not in coma. There was a strong correlation (r=0.89, p<0.01) between the grade of hepatic coma and CSF IAA. These data indicate that there is an association between elevated CNS tryptamine metabolism and hepatic coma. How far changes in the metabolism of tryptamine and other trace amines are relevant to the induction of hepatic coma or are simply a reflection of advanced liver dysfunction is unclear.     

Electric stimulation and insulin coma

Summary Observations with nonconvulsive stimulation during insulin coma have been presented. The method is useful in arousing patients from coma, provided that they have not entered a deep phase. Adrenalin and blood sugar responses suggest that activation of the diencephalic pituitary-adrenal axis occurs. The theory that during insulin coma a successive inactivation of phylogenetic layers within the brain takes place is supported by the observations reported here. Therapeutic results suggest a favorable comparison with deep insulin coma, provided a differential and dynamic approach is followed. Complications, such as delayed and protracted coma, have not been encountered. Treatment time is shortened to about two hours, and the average number of treatments is about 40.Read at the 109th annual meeting of the American Psychiatric Association at Los Angeles, May 1953.     

Blink reflexes in severe traumatic coma.

Blink reflexes were studied in 21 patients in coma after severe head injury. Our observations suggest that blink reflexes are a simple, objective, neurophysiological test to evaluate brainstem function. Correlations between these reflexes and the anatomoclinical stanges of coma and the Glasgow coma scale have been established. Presence of the early R1 component shows the integrity of at least a part of the pontine structures. The appearance of the late R2 component is correlated with a better chance of recovery from coma.     

Alpha coma

Six personal cases of alpha coma are reported: 3 following a cerebrovascular accident and 3 resulting from cerebral concussion. Two patients survived. On the basis of differences in pathogenesis, EEG characteristics and prognosis, the following classification is proposed: alpha coma resulting from brain stem vascular accident; cerebral concussion; diffuse cerebral hypoxia; drug intoxication. The clinical course of each of the classes of alpha coma is outlined. The alpha coma state is not restricted to cases with structural brain stem lesions c.q. lesions of the pontomesencephalic region.     

The EEG in metabolic encephalopathy and coma.

Excellent early work on stupor and coma can be found (particularly with regard to anoxia) in the work of Fischgold and Mathis (1959) in France, and Pamela Prior in England (1973a). These workers correlated deepening levels of coma with particular EEG patterns, and the suppression of EEG reactivity. Alpha frequency patterns in coma (alpha coma), spindle-like sleep patterns in coma (spindle coma) and "triphasic waves" are among the wide variety of endocrine disorders discussed in case reports and series leading to identification of particular EEG patterns. EEG correlations with prognosis are most reliable with cardiorespiratory arrest (CRA) with its consequent anoxic-ischemic insult. If etiology is known, EEG can often be a reliable predictor of outcome. EEG usually has little specificity with regards to etiology, but some patterns do favor particular diagnoses: for example, triphasic waves (TWs) are frequently seen with hepatic and renal insufficiency in young adults; spindle coma patterns are believed to indicate dysfunction at the brainstem level (Chatrian, 1990). EEG is most useful in differentiating organic from psychiatric conditions, in excluding nonconvulsive status epilepticus (NCSE), and in providing a rough guide as to the degree of cortical and subcortical dysfunction.     

P300在鉴别闭合性颅脑外伤患者真假昏迷的价值

目的：研究P300在鉴别闭合性颅脑外伤患者真假昏迷的价值。方法：将237例闭合性颅脑外伤患者根据其有否昏迷史分为有昏迷组,无昏迷组,假昏迷组及不详组,并对各组视觉（图像）刺激诱发的异常P300波潜伏期和波幅进行比较分析。结果：昏迷组与无昏迷组的P300潜伏期和波幅有非常显著的差异（P＜0．001）;昏迷组与假昏迷的P300潜伏期和波幅亦有非常显著的差异（P＜0．001）;但无昏迷组与假昏迷组间无明显差异（P＞0．05）;昏迷史不详组与无昏迷组间有显著差异（P＜0．05）。结论P300波的变化可作为判断闭合性颅脑外伤患者有无昏迷的一项客观指标,在外伤事故鉴定中有重要的参考价值。     

Immediate coma and poor outcome in subarachnoid haemorrhage are independently associated with an aneurysmal origin

Objective

Subarachnoid haemorrhage (SAH) may present with coma and this is known to be associated with aneurysmal origin and blood load. Aneurysmal origin is associated with increased blood load and existing data do not allow us to determine if the association between coma and aneurysmal SAH is wholly due to blood load or if aneurysmal origin has an additional independent effect. The objective of our study is to find if an aneurysmal origin is a predictor of acute onset of coma independent of blood load.

Methods

A series of consecutive patients with spontaneous SAH were divided into two groups: aneurysmal (aSAH) and non-aneurysmal – angiographically negative SAH (naSAH). Blood load was quantified so that the effect of aneurysmal origin could be resolved from the effect of the amount of blood spilled. Non-parametric regression was used to relate blood load to coma and poor outcome rates for aneurysmal bleeds.

Results

We analysed a total of 421 patients presenting during the period 2009–2011. Ninety aneurysmal cases presented with coma, seventy immediately in the early phase and seven shortly after rebleeding. None of the naSAH cases presented with immediate coma and 1 developed delayed coma. Delayed coma was associated with acute hydrocephalus in both groups. Aneurysmal origin was found to be an independent determinant of immediate coma (p = 0.02) and poor outcome (p < 0.001).

Conclusion

Immediate coma and poor outcome in SAH are associated with an aneurysmal origin and do not characterize naSAH.     

Computed tomography findings in thiamine deficiency-induced coma

Although brain magnetic resonance imaging is a more sensitive diagnostic tool in the evaluation of coma, noncontrast head computed tomography (CT) may demonstrate highly specific findings in some cases of coma. We present a case of thiamine deficiency-induced coma associated with acute necrosis of fornices documented on CT and review cardinal neuroimaging features of Wernicke encephalopathy. Acute fornices necrosis is a novel finding on head CT suggestive of thiamine deficiency.     

Nontraumatic coma. Glasgow coma score and coma etiology as predictors of 2-week outcome

In 1987 and 1988, we carried out a prospective study of patients older than 10 years with nontraumatic coma in the intensive care units of Columbia-Presbyterian Medical Center, New York, NY. Of 188 patients with Glasgow Coma Scale (GCS) determinations within 72 hours, 61% were dead or in persistent coma by 2 weeks from onset. Age, sex, and ethnicity did not influence outcome. The 2-week outcome for patients with initial GCS of 3 to 5 was 14.8% awake; 85.2% were dead or in persistent coma. For the GCS 6 to 8 group, 53.1% were awake and 46.9% were dead or in persistent coma. Hypoxic or ischemic coma had the worst 2-week outcome (79% dead or comatose); coma caused by metabolic disease or sepsis (68%), focal cerebral lesions (66%), and general cerebral diseases (55%) were intermediate, while drug-induced coma had a favorable outcome (27% dead or comatose). The independent predictors of 2-week outcome were the first GCS and drug-induced coma. The predicted probability of waking at 2 weeks was eight times better for drug-induced coma than other causes when GCS was held constant. Patients with an initial GCS score of 6 to 8 were seven times more likely to waken than those with a score of 3 to 5. The motor subscore alone was a significant independent predictor of 2-week outcome. Modification of coma score to include etiology may give more accurate predictions of 2-week outcome after nontraumatic coma.     

Rhythmic delta activity represents a form of nonconvulsive status epilepticus in anti-NMDA receptor antibody encephalitis

Anti-NMDA receptor antibody encephalitis is a limbic encephalitis with psychiatric manifestations, abnormal movements, coma, and seizures. The coma and abnormal movements are not typically attributed to seizure activity, and slow activity is the most common EEG finding. We report drug-resistant nonconvulsive status epilepticus as the basis for coma in a 19-year-old woman with anti-NMDA receptor antibodies and a mediastinal teratoma. The EEG showed generalized rhythmic delta activity, with evolution in morphology, frequency, and field typical of nonconvulsive status epilepticus. The status was refractory to antiepileptic drugs, repeated drug-induced coma, resection of the tumor, intravenous steroids, rituximab, and plasmapheresis. She awoke after the addition of felbamate, and the rhythmic delta activity ceased. The rhythmic delta activity described with coma in anti-NMDA receptor antibody encephalitis may represent a pattern of status epilepticus in some patients. Felbamate, which has NMDA receptor antagonist activity, should be studied as a therapeutic agent in this condition.     

Alpha coma: rectrospective presentation of 20 cases

Alpha coma is a relatively rare variety of EEG resulting from diffuse cerebral anoxia, focal brainstem lesions, metabolic disturbances or intoxications. It is a monotonous, unreactive and anteriorly predominant activity of less than 50 microV and of 8 to 13 Hz. Twenty cases of alpha coma are reported: 16 resulting from anoxic encephalopathy, 2 from brain stem strokes, and 2 from metabolic encephalopathy. Cardiac arrest was the main cause of alpha coma (10 cases); a large number of patients (7 cases) died, or have survived with severe neurologic deficits (2 cases). In 2 cases there was a metabolic-toxic cause (benzodiazepines and parathion intoxication). The 2 patients with pontomesencephalic haemorrhage died. The physiopathogenicity of alpha coma, which remains obscure, is also discussed.