Klazomania

Klazomania (from the Greek "klazo"-to scream) refers to compulsive shouting; it can be a complex tic, similar to echolalia, palilalia and coprolalia, although this classification is somewhat difficult because tic disorders "may be challenging to differentiate from compulsions".

Klazomania can be a symptom of Tourette syndrome (TS), Asperger syndrome (AS), autism and encephalitis lethargica; it has also been seen in people with alcohol abuse and carbon monoxide poisoning. It was first reported by L. Benedek in 1925 in a patient with postencephalitic parkinsonism.

Classification

Klazomania can be classified as a tic with similar neural activity to other tic disorders including Tourette syndrome. Compulsions are a result of an obsessive thought that brings mental anxiety if the thought is not acted upon. Compulsions and complex tics, such as klazomania, are difficult to differentiate from each other and share some similar neural pathophysiology. Disorders where compulsive behavior is exhibited are obsessive-compulsive disorder (OCD) and autism.

Signs and symptoms

Klazomania is similar to other complex tics including echolalia, palilalia and coprolalia. It is characterized by compulsive shouting, which can be in the form of swearing, grunting or even barking. The subject may appear flushed, and klazomania can occur with increasing frequency if the person is agitated. The duration of the incident depends on the individual, but it can be characterized by a peak period, followed by intermittent remissions of less intensity. Although the individual may sound like they are in pain, there does not appear to be any actual physical discomfort. The shouting can be accompanied by other symptoms, such as oculogyric crises or other involuntary movements. Klazomania is comparable to temporal lobe epilepsy, although the two can be distinguished by the duration of the attack and the fact that the patient experiencing klazomania appears to retain consciousness.

A 1961 report desribed a postman known as K.R. who contracted encephalitis lethargica at the age of 12. While he reported no significant ill effects from the disease, he was irritable and complained of fatigue for years after recovering. At 22, the patient received a head injury, though he did not sustain a concussion or cranial fracture from the incident. Six months later, he developed oculogyric spasms, as well as dyskinesias of the mouth and tongue. In 1957, at the age of 44, the patient experienced his first bout of klazomania while working in the post office. He remained conscious for the entire incident, while he shouted for about half an hour and appeared "crazy" for hours after the shouting ended. The next day, he felt better, though he did report being tired. The patient continued to suffer from the attacks for the next few years before coming under observation of Wohlfart and colleagues. He subsequently served as a model to describe klazomania from beginning to end.

As seen in K.R., the onset was characterized by absentmindedness: the patient stared straight ahead and only responded in monosyllables in the minutes leading up to the incident. An oculogyric spasm then developed, during which he demonstrated echolalia. After 15 minutes, further motor symptoms arose, with the patient making small jerky motions with his arms that developed into larger, circular movements. At 20 minutes, the attack reached its peak, with the patient becoming bright red and making large compulsive movements with his arms and kicking his legs. He began swearing, shouting, screaming, grunting and barking loudly, with intermittent bouts of heavy panting. He remarked upon the people present, with his comments being related to the situation in question. He attempted at times to excuse his behavior. Afterwards the patient was able to provide an account of what had happened. Wohlfart et al. concluded that the patient was aware of his surroundings during the attack, with the patient even expressing concern over missing a scheduled appointment; the patient demonstrated some ability to control his behavior when spoken to in a sharp tone, but he would inevitably return to his shouting and movements after a few seconds of stillness. The attack was accompanied by salivation, sweating, and tachycardia. The peak of the attack lasted 30 minutes; the intensity then started to subside, though the patient presented with intermittent remissions. The entire episode lasted an hour and a half from its onset.

Causes

Although the cause of klazomania is unknown, researchers have hypothesized that klazomania is caused by an irritating lesion in the mesencephalon. It is believed that there is a malfunction in the control of the motor circuit from the substantia nigra in the mesencephalon to the globus pallidus in the striatum (mesostraital pathway). This circuit becomes overstimulated during a mesencephalic "fit", which could be caused by tumors in the posterior fossa comprised of the cerebellum, medulla, and pons.

Studies have shown that klazomania is similar to Tourette syndrome and obsessive-compulsive disorder, which involve tics and compulsions. Tics and compulsions are dysfunctions in self-regulatory control of habitual behaviors. Tics and compulsions are controlled by cortical striatal thalamic cortical circuits (CSTC circuits).

Alcoholism and infections such as encephalitis are accompanied by phonic tics and occasionally klazomania. It is hypothesized that the cause of klazomania is linked to the brain damage due to alcoholism or encephalitis.

Pathophysiology

Using fMRI neuroimaging researchers have identified areas of the brain that are activated prior to and during the onset of tic activities. Researchers coordinated fMRI scans with the exhibition of tics and found that there was activation of paralimbic networks involving the anterior cingulate cortex, insular cortex, and the parietal operculum prior to tic onset. The strong activation of paralimbic areas and parietal operculum preceding tics in the present study suggests the role of this network as a potential source for the uncomfortable feelings associated with urges of tics. Future studies may clarify whether subtypes of tics and compulsions are generated differentially in these brain networks.

Changes are observed on EEG in the substantia nigra and the globus pallidus with klazomania. The mesostriatal pathway involving the substantia nigra and the globus pallidus are both dopaminergic pathways, and therefore it is believed that dopamine is one of the main neurotransmitters involved in klazomania. This belief is corroborated by the fact that dopamine antagonists, such as haloperidol, alleviate the symptoms of klazomania by blocking dopamine activity. Other brain abnormalities discovered with an EEG include slight cortical atrophy and a marginally enlarged lateral ventricle.

One hypothesis is that klazomania originates in the periaqueductal gray matter in the mesencephalon. The vocalizing center in animals is located in the periaqueductal gray matter and a klazomania-like episode involving grunts and animal sounds can be evoked by electrical stimulation of this region. This phenomenon can be linked to klazomania if it can be proved that humans also possess this vocalizing center.

Researchers have hypothesized that the stimulation of the autonomic nervous system by the posterior hypothalamus is involved in klazomania. Klazomania resembles sham rage in animals, which is controlled by stimulation of the sympathetic nervous system. During klazomania, a person may experience pupil dilation, tachycardia, salivation, increased blood pressure, retraction of lips, barking, grunting, and rage just as an animal would if presenting sham rage.

Brain structures implicated in Tourette's syndrome

The prefrontal cortex projects to the globus pallidus and caudate nucleus in the striatum, which projects to the thalamus, and finally back to the primary motor cortex to generate a behavior. The prefrontal cortex normally controls the stimulation and inhibition of the striatum and its motor output. However, the dysfunction of this fronto-striatal circuit leads to tics and compulsions because the prefrontal cortex cannot efficiently inhibit motor behaviors. There are two pathways that make up the CSTC circuits. The direct pathway originates in the cortex, which sends an excitatory signal to the neurons with D1 receptors (dopamine receptors) in the striatum. The striatum sends gabaergic input to the globus pallidus interna and the substantia nigra, which disinhibits the inhibitory signal sent to the thalamus. The thalamus then sends a disinhibited excitatory signal to the primary motor cortex in the frontal cortex and produces an involuntary motor movement, like excessive screaming in klazomania or any other tic. The indirect pathway also begins in the cortex, where the excitatory neurons synapse on the neurons in the striatum, which have D2 dopamine receptors. When overactivated, these D2 receptors cause less inhibition by the gabaergic neurons projecting from the striatum. These disinhibited neurons then send a weaker inhibitory gabaergic signal to the globus pallidus externa, which send a stronger inhibitory signal to glutamatergic neurons in the subthalamic nuclei. These glutamatergic neurons are more inhibited and send a weaker excitatory signal to the gabaergic neurons in the globus pallidus interna and the substantia nigra. These structures then cannot inhibit the thalamus as well and therefore cannot inhibit the motor output the thalamus sends to the primary motor cortex. The overstimulation of the cortex in both of these pathways leads to the expression of tics and compulsions, and possibly klazomania. The stimulation of these same circuits are also probably the cause of other complex phonic tics such as echolalia, palilalia, lexilalia, and coprolalia.

Management

Further information: [[:Treatment of Tourette syndrome]]

A variety of drug therapies have been used to treat klazomania. In large doses, atropine sulfate helps control the involuntary movements associated with klazomania. Attempts to treat klazomania with a combination of phenobarbital and trihexyphenidyl (also known as Artane) have been made. Phenobarbital acts as an anticonvulsant and is generally used to treat seizures, while Artane is used to treat involuntary movements in Parkinson's disease; however, this combination was found to have no beneficial effect in treating klazomania.

The classes of medication with the most proven efficacy in treating tics—typical and atypical neuroleptics including risperidone (Risperdal), ziprasidone (Geodon), haloperidol (Haldol), pimozide (Orap) and fluphenazine (Prolixin)—can have long-term and short-term adverse effects. The antihypertensive agents, clonidine (Catapres) and guanfacine (Tenex), are also used to treat tics; studies show variable efficacy, but a lower side effect profile than the neuroleptics. Clomipramine (Anafranil), a tricyclic antidepressant, and SSRIs—a class of antidepressants including fluoxetine (Prozac), sertraline (Zoloft), and fluvoxamine (Luvox)—may be prescribed when an individual also has symptoms of obsessive–compulsive disorder.

Deep brain stimulation has been used in treating a few patients with severe TS, but is regarded as an experimental and dangerous procedure that is unlikely to become widespread. The procedure is well tolerated, but complications include "short battery life, abrupt symptom worsening upon cessation of stimulation, hypomanic or manic conversion, and the significant time and effort involved in optimizing stimulation parameters". Individuals with klazomania could potentially benefit from DBS. but "only patients with severe, debilitating, and treatment-refractory illness should be considered; while those with severe personality disorders and substance abuse problems should be excluded."

Behavioral therapy has been examined as a form of treatment; however, for the most part, such therapies have not been evaluated.

History

The word "klazomania" comes from the Greek "klazo", meaning to scream. The term was coined by L. Benedek in 1925 when he witnessed bouts of compulsive shouting in a patient with postencephalitic parkinsonism. He reported that the attacks would last for up to several hours and seemed to be outside of the patient's control. He characterized the shouting as extremely loud, noting that it could be in the form of syllables, vowels or even animal noises. In addition, he observed that while the nature of the shouting could suggest that the patient was in pain, the sounds themselves were unrelated to any physical discomfort. He stated that the patient appeared to have the ability to anticipate an incident and could even prevent it through deep and rapid breathing. However, he noted that the effort required to suppress klazomania could be even more tiring than enduring it. He said that though anxiety could increase the frequency of klazomania, it did not affect the overall presentation.

Two of Benedek’s colleagues, E. Von Thurzó and T. Katona, recorded two further instances of klazomania in 1927. They expanded upon Benedek’s earlier observations, describing the angry flushed face of one patient, as well as extreme restlessness and agitation. They noted that afterwards the patient apologized for the incident, suggesting awareness of the behavior. From this, Thurzó and Katona proposed that there is no loss of consciousness during klazomania and that individuals may remain fully aware of their surroundings.

In 1961, Gunnar Wohlfart et al. reported a case of klazomania accompanied by oculogyric crises, another symptom of postencephalitic Parkinsonian syndrome. Klazomania was proposed to be associated with chronic alcohol abuse and carbon monoxide poisoning in 1996. Bates et al. reported on a 63-year-old who was admitted to a psychiatric hospital with a two-year history of sudden episodes of shouting. The man claimed to have no memory of the attacks, which he could anticipate by a few seconds. The episodes were characterized by shouting of "aagh" or "help" and he was reported to appear angry during the incidences. At the end of the outbursts he would appear surprised, though he was able to continue a conversation. The patient remained fully oriented between attacks. The episodes themselves occurred at a frequency of one or two a month, generally taking place in the evening and they got progressively worse from the time of their first presentation.

Research directions

While klazomania is associated with other complex phonic tics, research focused on the disease has suggested that the rare brain inflammatory disease encephalitis lethargica—and only a few individuals diagnosed with encephalitis lethargica placed under research observation—have exhibited klazomaniac symptoms; individuals suffering from a form of encephalitis also exhibited compulsive shouting (along with other behavioral disorders) as an apparent result of this neurological disease.

Research on klazomania is scarce. The demand for research for klazomania may not be as high as for other tics due to the relatively few cases of the symptom recorded, and further discouraged due to the overlap of klazomania symptoms with other tics of Tourette syndrome and other more common phonic tic disorders. Finally, difficulties in the passage of drugs through the blood brain barrier makes studying treatment possibilities for klazomania challenging.

Although specific current research on compulsive shouting is scarce, there are many ongoing studies and potential future studies on Tourette syndrome and other similar neurological disorders associated with complex phonic tics and behavioral compulsions similar to those of klazomania. Research methodology includes clinical trials, neuroimaging studies, post mortem brain autopsy, genome screening, and epidemiological studies.