Intratympanic therapy for Ménière's disease. High-concentration gentamicin with round-window protection.

Many therapeutic options exist for the management of patients with Ménière's disease. In the last few years, the use of intratympanic gentamicin has been investigated as an alternative treatment to vestibular nerve section or labyrinthectomy. In humans, the concentration of gentamicin used for intratympanic treatment of vertigo ranges from 10 mg/mL to 40 mg/mL, and the number of doses from 2 to 14, with a total administered amount between 6 and 2.400 mg. Here lower doses of gentamicin were used, usually had the lowest incidence of hearing loss, but more injections were needed to ablate vestibular function. The purpose of this study was to evaluate the acute and chronic ototoxic effects of intratympanic high-concentration gentamicin after having obliterated the round-window niche with connective tissue in 11 subjects' ears with Ménière's disease. Intratympanic gentamicin was administered according to a predetermined and fixed schedule consisting of two doses of 0.5 mL gentamicin solution, injected once a week with a drug concentration of 80 mg/mL. The total dose of gentamicin was < or = 80 mg. The charts of the patients were surveyed in accordance with the 1995 AAO-HNS guidelines. Three patients had recurrence of vertigo between 3 and 6 months after the second injection and went on to one additional dose of gentamicin. At 2 years follow-up, 10 patients (91%) had complete and 1 (9%) substantial control of vertigo; 3 subjects (27%) had hearing decreased. Tinnitus disappeared or decreased in 3 patients (27%); eight subjects (73%) reported their aural pressure abolished or decreased. The present study demonstrates that in patients with Ménière's disease, 0.5 mL gentamicin solution, with a concentration of 80 mg/mL (total dose < or = 80 mg), injected intratympanically once a week after having obliterated the round-window niche, permits complete or substantial control of vertigo in two-thirds of cases after two doses and in all subjects after three doses. This vertigo control rate is compared to that observed after vestibular nerve section. Hearing results are not different from those with natural control, with endolymphatic sac surgery, and with vestibular nerve section.

CBF changes during headache-free periods and spontaneous/induced attacks in migraine with and without aura: a TCD and SPECT comparison study.

BACKGROUND: The aim of the present study was to compare cranial arteries blood flow velocity as measured by means of transcranial Doppler sonography (TCD) with mean regional cerebral blood flow (rCBF) as measured by means of single photon emission computed tomography (SPECT) in migraine with and without aura during headache-free periods and spontaneous and/or induced attacks. METHODS: Regional cerebral blood flow (rCBF) and systematic ultrasonic Doppler flow were studied by Technetium-99m hexamethylpropilaminoxime (99mTc-HM-PAO) single photon emission computed tomography (SPECT) and transcranial Doppler sonography (TCD) respectively in controls (n=14) and in migraine with (n=13) and without aura (n=35) during headache free-intervals and spontaneous/histamine-induced attacks. RESULTS: In the migraine without aura group, Doppler flow examinations of the common carotid artery, external and internal carotid artery, ophthalmic artery and middle cerebral artery bilaterally did not reveal significant changes as compared with controls. During attacks, TCD examinations showed a moderate, although not statistically significant, reduction of blood flow velocity in the middle cerebral artery and in the internal carotid artery bilaterally as related to the interictal phase, concomitant with an increase of the flow velocity in the ophthalmic and external carotid artery. SPECT of these patients did not show, on the average, rCBF asymmetries during pain-free periods, although positive findings (i.e., focal hypoperfusion) were found in approximately half of the cases. During attacks, 74% of patients displayed a unilateral hypoperfusion, mainly in the occipital region. Low-flow areas were generally but not always consistent with the site of pain. In the migraine with aura group, significant reduction of blood flow velocity in middle cerebral artery was recorded by TCD on the affected side during attacks, as compared with the pain-free side. Hypoperfusion was registered between attacks by SPECT in approximately 2/3 of the patients. During attacks, a marked reduction of rCBF occurred in most patients (85%), mainly in the parieto-occipital region. The posterior rCBF asymmetries revealed at the SPECT and consistent with the general reduction of blood flow velocity documented by TCD may be related to cerebrovascular tone instability. CONCLUSIONS: Our findings do not support the paradigm that migraine with and without aura are two different entities.

In vitro activity of acetylsalicylic acid on replication of varicella-zoster virus.

Topical application of a mixture of acetylsalicylic acid (ASA) and diethyl ether is effective in the treatment of acute herpes zoster and postherpetic neuralgia. To study whether the other-than-analgesic effects of that treatment could be due to an antiviral activity of ASA the effects of the drug on the replication of varicella zoster virus (VZV) were assessed by the fluorescent focus assay on MRC5 and Vero cells. ASA caused a marked reduction in the spread of infection in MRC5 monolayers while in growing Vero cells the effective dose proved toxic. ASA concentrations (5-10 mM) which were effective in vitro against VZV are higher than the plasma concentrations attained in the standard treatment of chronic inflammatory states, but are consistent with the skin concentration attained by topical application of ASA/diethyl ether mixture. These data support similar findings relating the antiviral activity of acetylsalicylic acid to influenza virus, CMV, and HIV.

Skin and plasma levels of acetylsalicylic acid: a comparison between topical aspirin/diethyl ether mixture and oral aspirin in acute herpes zoster and postherpetic neuralgia.

OBJECTIVE: The aim of this investigation was to elucidate whether the analgesic effect was due to the local aspirin or to the systemic drug. This was done by comparing skin and plasma levels of acetylsalicylic acid (ASA) and salicylic acid (SA) after topically administered ASA/diethyl ether (ADE) mixture in acute herpetic neuralgia (AHN) and postherpetic neuralgia (PHN). The analgesia and the plasma and skin levels of ASA were also determined after oral administration of aspirin. METHODS: Nineteen patients, 11 (57.9%) with AHN and 8 (42.1 %) with PHN were given, on different days, a single 500-mg oral dose of ASA or a topical dose (750 mg) of (ADE) daubed onto the painful skin. The analgesic effect was assessed by means of a visual analogue scale (VAS). Overall pain relief was graded as: excellent, good, fair, or poor. AHN as well as PHN patients had severe pain at baseline (6.83 and 5.93). Levels of ASA and SA in plasma and in the stratum corneum after adhesive tape stripping of the treated area were determined by HPLC. RESULTS: After ADE application, the analgesic effect was very rapid and VAS scores were lower than at baseline. Pain significantly decreased by 82.6% after topical and 15.4% after oral ASA. After ADE, 95% of the patients had excellent or good pain relief, but after oral administration 79% of the patients had a poor response. Pain relief was similar in the two subgroups after ADE. Skin concentrations of ASA, but not of SA, after ADE were about 80- to 100-fold those after oral administration. Levels of ASA and SA in plasma after oral administration were similar to those previously found, but after ADE were undetectable or very low. Patients with excellent pain relief showed a trend towards higher ASA skin concentrations. CONCLUSIONS: The analgesic effect can be obtained only after topical administration, because by this route the skin levels of ASA are much higher than after oral administration. The mechanism is exclusively local; there are no active drugs in plasma after topical administration.

Determination of acetylsalicylic acid and salicylic acid in skin and plasma by high-performance liquid chromatography.

This study describes a HPLC method to determine the concentrations of acetylsalicylic acid (ASA) and salicylic acid (SA) in human stratum corneum and in plasma. The stratum corneum layers for ASA/SA analysis were removed from three patients with postherpetic hyperalgesia treated with topical and oral aspirin. Blood samples were also collected from the same patients. Tape strippings were placed in acetonitrile and sonicated for 15 min. After centrifuging, aliquots of the supernatant were injected into the chromatograph. ASA and SA from plasma samples were extracted on Isolute C8 columns. Due to interfering peaks in the tape samples, HPLC conditions were slightly different for tape and plasma samples. ASA and SA were separated on a LiChrospher 100 RP-18 column at 1 ml/min using a water-phosphate buffer (pH 2.5)-acetonitrile mobile phase (35:40:25, v/v/v). A linear response to quantities of ASA from 0.1 to 100 microg/cm2 and of SA from 0.1 to 5 microg/cm2 in tape and to quantities of ASA 0.1 to 2 microg/ml and 1 to 50 microg/ml was obtained and the recovery from tape and plasma samples was over 98%. The method is sensitive (0.1 microg/cm2) and specific enough to allow the determination of the drugs in the skin not only after topical but also after oral administration. A good sensitivity was also obtained in plasma (0.1 microg/ml) allowing study of the kinetics of ASA and SA in plasma after oral administration. Concentrations of ASA after topical administration were 100-200 times higher than after oral administration. Plasma levels of ASA and SA after oral administration were similar to those previously found. No ASA or SA were detected in plasma after topical ASA administration.

SUNCT syndrome associated with cavernous angioma of the brain stem.

A 62-year-old male patient with 2 years of SUNCT syndrome is described. The patient presented with long-lasting periods of frequent attacks of intense orbital pain with a duration of about 1 min, associated with ipsilateral conjunctival injection, lacrimation and rhinorrhea. Cranial MRI and cerebral angiography demonstrated an ipsilateral cavernous angioma of the pons, involving the trigeminal roots. As the pain was refractory to most treatments, including carbamazepine, the patient asked for, and eventually underwent, direct surgical excision of the malformation. Following the operation, his neurological conditions rapidly deteriorated and he died of postoperative complications (haemorrhage).

Hypnosis and spasmodic torticollis--report of four cases: a brief communication.

Dystonia and particularly spasmodic torticollis are neuromuscular disorders that are extremely resistant to most therapies (physical, medical, or surgical). Torticollis is a unilateral spasm of the neck muscles, particularly of the sternocleidomastoid, that produces violent, tonic turning of the head to one side. The etiology remains uncertain, although the role of psychogenic factors has been emphasized. This article reviews the literature and reports four cases of spasmodic torticollis treated successfully with hypnosis. In all four cases, psychogenic causes were involved. Postural hypnosis (i.e., hypnosis in the standing position) was employed to counteract and minimize muscle spasms due to postural reflexes. A hypnobehavioral approach was adopted along with hypnotic strategies that included hierarchical desensitization, sensory-imaging conditioning, ego-boosting suggestions, and hypnosis-facilitated differential muscle retraining. In two cases, a combined hypnosis and electromyographic-biofeedback approach was used to equilibrate and retrain affected neck muscles. Although the hypnotherapeutic process took several months to induce and stabilize significant changes, outcome results were good to excellent in all cases, with marked reduction of the torticollis and the hypertrophy of the neck muscles as well as a reduced interference of symptoms in daily living.

Postoperative pain in neurosurgery: a pilot study in brain surgery.

The incidence, magnitude, and duration of acute pain experienced by neurosurgical patients after various brain operations are not precisely known, because of a lack of well-designed clinical and epidemiological studies. We assessed these important pain variables in 37 consecutive patients who underwent various brain neurosurgical procedures. Postoperative pain was more common than generally assumed (60%). In two-thirds of the patients with postoperative pain, the intensity was moderate to severe. Pain most frequently occurred within the first 48 hours after surgery, but a significant number of patients endured pain for longer periods. Pain was predominantly superficial (86%), suggesting somatic rather than visceral origin and possibly involving pericranial muscles and soft tissues. Subtemporal and suboccipital surgical routes yielded the highest incidence of postoperative pain. Age and sex were significantly associated with the onset of pain, with female and younger patients reporting higher percentages of postoperative pain. Psychological Minnesota Multiphasic Personality Inventory profiles of patients with and without pain significantly differed on the Hypochondriasis scale, with patients without pain scoring unexpectedly higher than patients with pain. It is possible that hypochondriasis serves as a defense mechanism against pain, at least in some patients. Results of this pilot study indicate that postoperative pain after brain surgery is an important, although neglected, clinical problem, that deserves greater attention by surgical teams, to provide better and more appropriate treatment.

Magnetic resonance imaging in migraine and tension-type headache.

Cerebral magnetic resonance imaging was performed on 63 patients with chronic primary headache (28 with migraine with and without aura, 35 with tension-type headache). Fifty-four headache-free individuals of the same age range were used as controls. The headache sufferers showed an incidence of focal white matter abnormalities on T2-weighted magnetic resonance imaging significantly higher than the age-matched control group (33.3% vs 7.4%). The incidence of white matter abnormalities did not correlate with age (except for patients older than 60 years), sex, headache history, headache status, or ergotamine consumption. Migraine (with and without aura) and tension-type headache patients had similar prevalence of white matter abnormalities (32.1% vs 34.3%). The lesions were predominantly distributed in the frontal region, independent of the side of usual aura or headache. Our findings indicate that both migraine and tension-type headache may be associated with early pathologic changes in the brain and may share, at least in part, common pathogenic pathways.

Doppler analysis of pulmonary venous flow in left atrial myxoma.

In a patient with obstructive left atrial myxoma, we analyzed by pulsed Doppler echocardiography the flow pattern through the mitral valve and in the pulmonary veins. Two mitral flow patterns were observed: the first was present near the medial commissure and along the anterior leaflet and was characterized by the absence of mid-to-late diastolic filling flow; the second was found near the lateral commissure and was characterized by the obstruction of mid-to-late diastolic filling flow, mimicking mitral stenosis. The pulmonary vein flow showed brief and rapidly decelerating anterograde diastolic flow wave and an early systolic retrograde flow wave. These waves were respectively related to the diastolic forward and the systolic backward movement of the tumor. This case report shows that pulmonary vein flow analysis may give new insights into left atrial filling and emptying dynamics in left atrial myxoma.

[Herpetic vestibular neuronitis: a hypothesis]. / Neuronite vestibolare erpetica: un'ipotesi.

Abundant experimental research has shown the potentially damaging effects that the herpes simplex virus (HSV) may have on peripheral or central nervous pathways. Fifty subjects (ages 20-45) with labial herpes virus (HSV-1) and 15 (ages 25-35) with genital herpes virus (HSV-2) were studied through recording spontaneous and optokinetic nystagmus (OKN) and using the eye-tracking-test (ETT) by means of electronystagmography (ENG). Recording was carried out during the first two days after vesicular eruption and seven days later, when cutaneous manifestations had disappeared. Thirty-five of the 50 subjects with HSV-1 showed spontaneous nystagmus, frequently with a vertical component, which in most cases had disappeared by the seventh control day. We recorded qualitative alterations of OKN as well as ETT in 19 patients while in 3 subjects only ETT was abnormal. All the subjects were normal on the seventh control day. At no time did any of the patients with HSV-2 show objective signs involving the peripheral or central vestibular system. Our research shows that HSV infection, especially HSV-1 infection, determines subclinical alterations of the vestibular function, probably due to the involvement of the brainstem. Therefore the virus is to be taken into account in establishing the etiology of "unknown" vertigo.

[Visual inhibition of the ampullar rotational-acceleratory excitation]. / Inibizione visiva dell'eccitamento rotoacceleratorio ampollare.

We have studied in normal subjects, the monocular and binocular influence on the nystagmus provoked by angular acceleration. The results show that the fixation determines a reduction of all quantitative parameters of the nystagmic response that, in the binocular fixation condition, is nearly 80% and halves with monocular fixation. The data shows activity conditions in a simple summation report of the values of visual input and demonstrate not only that the quality of the visual inhibition is, in normal subjects, perfectly equivalent between the two eyes but also that the stimulations evoked in the two labyrinths, convergent to the equilibrium centres, integrate in a perfectly complementary way. We have to study how this complex and harmonious polysensorial activity deteriorates with pathologic alterations of the visual and ampullar systems.

Minor stressful life events (daily hassles) in chronic primary headache: relationship with MMPI personality patterns.

This study investigated the relationship between minor life events (i.e. daily hassles) and personality patterns from selected scales of MMPI in the persistence of primary headache in 83 patients. Comparisons between headache subgroups indicated that tension-type headache patients are much more likely than those with migraine to have experienced high level of microstress (hassles density), with mixed headache in between. Tension-type headache patients reported higher MMPI scores on scales 1, Hypochondriasis (somatic concern), scale 3, Hysteria (denial) and scale 7, Psychasthenia (anxiety), but not on scale 2 (Depression), than migrainous patients. In addition, individuals with high level of microstress appeared to be more depressed and anxious than low-stress headache patients, scoring significantly higher on MMPI scales 2 (Depression) and 7 (Psychasthenia). As no significant differences due to sex, age, headache history and status, except for the headache density (i.e. severity x frequency) appeared, it is likely that high-stress levels are due, at least in part, to greater density of pain, rather than to discrete headache syndromes. Our findings support the notion that depressed mood and anxiety may account for a third intervening variable in the relationship between chronic headache and life stress.

[Interaction between vision and vestibular nystagmus]. / Ricerche sull'interazione visiva del nistagmo vestibolare.

In order to assess the visuo-vestibular interaction and its behaviour in connection with the age, we have submitted 20 healthy subjects from two age groups ranging between 21-30 and 65-75 years of age to two rotation tests (with closed eyes and with opened eyes with fixation of a light). The results show a variation of the nystagmic response with fixation of about 60% in the young people and of about 40% in the elderly. These results demonstrate that the extent of the inhibition is dependent upon age and is less effective in the elderly.

[Experimental research on vestibular compensation using posturography]. / Richerche sperimentali sul compenso vestibolare mediante posturografia.

Vestibular compensation is a representation of nervous system plasticity which manifests as a gradual recovery of equilibrium function both in vestibulo-spinal system and vestibulo-oculomotor system. In order to assess whether the vestibular compensation is a homogeneous process among the different reflexes, the Authors have studied two groups of subjects affected by peripheral or central lesion. The development of the vestibular compensation has been evaluated by the rotation and posturographic tests. The results demonstrate a constant correlation between rotation and stabilometric parameters in the patients suffering from peripheral dizziness while there isn't any correlation between acceleratory and posturographic tests in patients affected by central vertigo. These results demonstrate that the compensation develops at the different levels of the balance function in a very different and independent way and that comparison of the rotation and posturographic patterns may be useful to establish the peripheral or central site of the lesions.

[Effect of aging on posture]. / Effetti della senescenza sulla postura.

In order to assess the postural behaviour of the elderly, we have submitted twenty subjects of more than seventy years old to posturography. In all cases, compared to young people, significant variations of the posturographic parameters regarding in a particular way the total tracing length, the ellipse surface and the mean speed have been recorded. The conclusion is that the values obtained should always be compared with the standard values for each age group.

[Experimental research on sensitized posturography: importance of the neck reflexes]. / Ricerche sperimentali sulla posturografia sensibilizzata: importanza dei riflessi cervicali.

In order to assess the influence of the cervical structures on the vestibulo-spinal reflex, and so on the posture, we have studied twenty subjects undergoing stimulation of the neck's proprioceptor structures. Each subject, by means of computerized stabilometric platform, has been submitted to the sensitized test with head retroflexed. In all cases significant variations of the posturographic parameters regarding in a particular way the total tracing length, the ellipse surface and the mean speed have been recorded. The results show that there are in man too stimulations of cervical origin which serve the purpose of maintaining posture; we can't exclude the possibility of the interference of an otolithic stimulation.

[Effect of the cervical reflex on the posture of normal subjects. Balance measurement study]. / Effetti dei riflessi cervicali sulla postura del soggetto normale. Ricerche stabilometriche.

The little we know about the existence and the meaning of the cervical component on the vestibulo-spinal reflex, led us to carry out a study on normal subjects examined by computerized stabilometry with the head turned 75 degrees left and right, in order to check the postural alterations during the stimulation of the neck proprioceptors. The results show a significant increase of the values of the LTT, SE and Vm with the head turned to the left; the increases were not significant with the head turned to the right. The difference is difficult to explain. The results show that in man too the posture is affected by reflex of cervical origin.

Auriculotemporal syndrome (Frey's syndrome) presenting as tic douloureux. Report of two cases.

Two cases of auriculotemporal nerve syndrome (Frey's syndrome) presenting as trigeminal tic douloureux are reported. This condition, characterized by gustatory sweating and facial hyperemia, is occasionally associated with pain, which is usually described as aching or burning, and long-lasting. In these two cases, however, a tantalizing gustatory pain occurred in excruciating brief paroxysms. The pathophysiology of the syndrome, with particular reference to pain, and possible treatment modalities are discussed.

[Stabilometry and definition of the threshold of galvanic vestibular stimulation in normal subjects: an experimental study]. / Stabilometria e definizione di soglia galvanica di eccitamento vestibolare nei soggetti normali: richerche sperimentali.

The effect of the galvanic stimulation on the vestibular apparatus has been evaluated by registration on the postural deviations, using a stabilometry platform. We have studied the galvanic body-sway responses in a group of normal subjects, using a binauricolar bipolar stimulation, with the electrodes attached by means of surgical tape to the mastoid area. The records of body-sway responses have demonstrated in 80% of the considered cases a significant variation of all positional parameters after a current intensity of 2 mA, according the body sways toward the positive stimulus. At the same current intensity only five of the studied subjects have shown multidirectional swinging, in three cases joined with a subjective slight sway toward the ear stimulated with positive polarity. Therefore the galvanic test, joined with the posturography, proves to be a useful auxiliary method in vestibular investigation, allowing us to lower the threshold of galvanic stimulation and to make the electric stimulus better supported for the patient.