Recent progress in the field of molecular biology and genetics has been remarkable, and has led to elucidation of the pathogenesis of various diseases and to the establishment of new treatments. Next-generation sequencing and epigenetics are playing the central role. Although the human genome project was completed with a large expenditure in terms of time and money of about 13 years and 300 billion yen in 2003, the entire genome could be decoded in about two months at the cost of about 120 million yen in 2007 by one individual, Dr. James Watson, who was a Nobel prize winner in the field. This is the next-generation sequencing technology, and since the speed of analysis increased by leaps and bounds, it had the ability to decode one set in the time that it previously took to decode 200-1000 type sets, and the cost also decreased sharply, analyses are progressing in various regions now. Epigenetics refers to a change of acquired (based on an environmental agent) genetic control without any change of he DNA sequence, and research has been prospering from around 2000. Typical epigenetic mechanisms include DNA methylation, histone modification, non-coding RNA, etc., and it is thought that these phenomena cooperate mutually, causing a change in the gene expression control and chromatin structure, and leading to differences of expression among individuals. The study on congenital hearing loss precedes genetic research in the field of Otorhinolaryngology, and this paper explains a part of it.
I investigated the contribution of sleep disorders in unidentified dizziness. In BPPV (Benign Paroxysmal Positional Vertigo) cases where the cause of the dizziness is to a certain degree clear, the average ESS (Epworth Sleepiness Scale) score was 14.9 points. On the other hand, the average score for dizziness in cases of unknown cause was 17.2 points. The ESS score in cases of dizziness of unknown cause was statistically significantly higher. Of the 77 cases with dizziness of unknown cause, Orthostatic dysregulation (OD)-positive accounted for 48 cases (62.3%) with high significance. Twenty-nine cases (37.7%) were negative. It was thought that OD is considered as being present together with sleep disorders in some of the cases that have been diagnosed with dizziness of unknown origin in outpatient care, and this should always be kept in mind.
We report herein on a case of disequilibrium due to central nervous disorders with a good response to acetazolamide. A 51-year-old woman presented with episodic disequilibrium and vertigo. Her symptoms began when she was a child. Her symptoms were worsened by positional change or physical exercise, lasting for several hours. She also had migraine-like headaches. Her family history was unremarkable. On examination, she showed gaze-evoked nystagmus, direction-fixed right beating positional nystagmus with down-beating nystagmus. Electronystagmography revealed saccadic pursuit, impaired optokinetic nystagmus, and disorders of visual suppression in caloric tests, suggesting central nervous disorders. MRI showed slight cerebellar atrophy without downward displacement of the cerebellar tonsil through the foramen magnum. Although she did not have family history, we clinically diagnosed her as having episodic ataxia type 2 (EA-2). She took acetazolamide (250 mg) per day. The frequency and intensity of her symptoms dramatically decreased. When we see a patient with episodic disequilibrium due to central nervous disorders, we should take EA-2 into account.
We report herein on a 16-year-old man with acute disseminated encephalomyelitis (ADEM) who presented with rotatory vertigo. Initially, we suspected a peripheral vertigo, such as Meniere's disease, because of the presence of direction-fixed right-beating horizontal-rotatory nystagmus and low-tone sensori-neural hearing loss in his right ear. The positional nystagmus, however, varied with time; left-beating horizontal-rotatory nystagmus was noted on the 2nd day and ageotrophic positional nystagmus on the 13th day of hospitalization. Enhanced brain MRI was performed, because the patient exhibited persistent gait disturbance and headache. High intensity area in FLAIR sequence and a ring-enhanced lesion were detected around the forth ventricle. The neurologist diagnosed ADEM based on the clinical symptoms, feature and course. No additional treatment was undertaken because the patient recovered spontaneously, and no recurrent symptoms have been observed. However, the ageotrophic positional nystagmus together with MRI lesion remained. It is important to suspect central vertigo such as ADEM, especially when the patient is young and shows gait disturbance.
We report herein on a 24-year-old male who complained of vertigo and tinnitus caused by cerebellar hemorrhage from an arteriovenous malformation (AVM). At his first visit to the emergency room of the Internal Medicine Department at our hospital, he complained of vertigo and transitory tinnitus, but he did not show any obvious cranial nerve symptoms. He was therefore diagnosed as having peripheral vertigo and treated with anti-motion sickness and antiemetic medicine. He came again the next day and was treated with fluid replacement and advised to consult the Department of Otolaryngology. Two days after the first visit, he consulted our otolaryngology outpatient clinic. He presented with rightward gaze and positional nystagmus, dysarthria, curtain sign, and pooling of saliva at the piriform recess. We consulted the Department of Neurosurgery, suspecting a central nervous system disorder. CT and MRI scans revealed a 4-cm cerebellar hemorrhage and a compressed third ventricle. Cerebral angiography revealed a 1-cm AVM in the cerebellum. Subsequently, resection of the AVM was performed. Twenty-six days after the first visit, although he still presented with rightward positional nystagmus, there was no gaze nystagmus and his caloric test was normal. Three months after the first visit, he presented with no positional nystagmus, but saccadic pursuit remained. Although cerebellar hemorrhage commonly presents with vertigo, vomiting, headache, and appendicular ataxia as the first symptoms, we experienced a case of cerebellar hemorrhage from an AVM without such symptoms but with vertigo and tinnitus.
I described how, as an otolaryngologist, I have assessed psychological factors such as depression in patients complaining of vertigo/dizziness. First of all, otolaryngologists need to clarify whether patients have somatic disorders using the latest techniques. And then, otolaryngologists should try to assess the extent of psychological factors associated with the patients' vertigo/dizziness. At the time of medical interviews, consistency of symptoms and signs as somatic disorders must be considered. After that, some questionnaires and mental tests are used. I always use the DHI (dizziness handicap inventory). Although this questionnaire is basically used for assessment of subjective impacts of dizziness/vertigo, it can reflect the psychological states of patients to some extent. The majority of patients with very high scores (DHI scores>80) had psychological problems. I recommend the POMS (profile of mood states) approach as a screening test of psychological problems because one can assess multiple factors associated with the patients' overall mental state. The SDS (self-rating depression scale) and the STAI (state-trait anxiety inventory) can be also used for assessment of depression and anxiety respectively. Although mental tests are useful for assessment of patients, one should not put too much faith on the results of a single mental test but assess patients comprehensively.
There are several treatment options for patients experiencing dizziness and depression. Two main therapeutic strategies are pharmacological and non-pharmacological. It is important to discern the various non-pharmacological therapies that can be used before using pharmacological therapy. Further, it is important to understand depression or anxiety in patients with dizziness, as these psychological states cause and exacerbate dizziness owing to vestibular dysfunction. Therefore, a good doctor-patient relationship is essential to treat patient with depression. To maintain a good relationship, doctors should speak and behave in an appropriate manner with their patients. Typically, patients can easily sense the doctor's anxiety to cope with and/or manage patients, and this has a negative effect on the patient-doctor relationship. Therefore, the confidence with which a doctor handles a particular case is important. Second, behavioral therapy such as vestibular rehabilitation, also aids pharmacological therapy. The main purpose of vestibular rehabilitation is to obtain vestibular compensation to stimulate the cerebellum. Vestibular rehabilitation can also be used as behavioral therapy to avoid inappropriate behavior and demonstrate appropriate behavior.
Patients with depression often complain of somatic symptoms like dizziness. It is very difficult to treat patients suffering from severe dizziness and depression with only anti-vertiginous-drugs. Therefore, using psychotropic drugs is one method to treat this type of patient. However, we believe that psychotropic drugs should be prescribed according to advice from psychiatrists or doctors who are familiar with these drugs, because benzodiazepine drugs can cause drug-dependence, anti-depressants exacerbate the condition in patients with irritability and psychiatric patients are at some risk of suicide. Physicians (non-expert psychiatrists) need to be careful when treating patients with depression when they prescribe psychotropic drugs, because these patients may become drug-dependent, more irritable and be at some risk of suicide. To reduce the risk of these incidents, physicians are strongly encouraged to consider introducing these patients with psychiatric disorders to psychiatrists. Recently, serotonin selective re-uptake inhibitors (SSRI), another kind of anti-depressant, have been prescribed more frequently by physicians. Our 33-year-old female case with severe dizziness and depression could be completely treated using SSRI. Using SSRI carefully can improve the mental condition and the quality of life (QOL) of patients who are suffering from severe dizziness and depression.
Dizziness is occasionally associated with depression; hence, it is necessary for otolaryngologists to gain a better understanding of depression. In this paper, we describe the interaction of depression and dizziness, and in the next, we will review the clinical practice points regarding depression. In order to diagnose depression, it is necessary to conduct an appropriate interview, including questions to establish the presence and chronology of specific depressive symptoms. Observation to identify the possible signs of depression is also important. With regard to medications, precautions should be taken particularly with patients receiving selective serotonin reuptake inhibitors (SSRIs), which may cause possible drug interactions and adverse reactions often observed during the period of therapeutic effects. Therefore, SSRIs should be prescribed with caution. During treatment, a good doctor-patient relationship is essential, and for successful treatment, patients should be kept completely informed about the disease, with some room left for diagnostic doubts. A doctor should assure patients, without making them impatient, that they will not be abandoned and that their condition will improve soon. When patients are referred to a mental health specialist, informed consent should be obtained, considering suicidal tendencies. Finally, the feasibility of physical therapy for depression has been discussed here. Combined psychological and physical methods for the treatment of dizziness can also aid in ameliorating comorbid depression.