Unilateral INO is associated with ocular tilt reaction in pontomesencephalic lesions: INO plus.

OBJECTIVE: Correlation of internuclear ophthalmoplegia (INO) with components of the ocular tilt reaction (OTR) in order to localize graviceptive (specifically otolithic) pathways in the brainstem. METHODS: We retrospectively analyzed data of 120 patients with INO (87 unilateral [9 of whom had one-and-a-half syndrome], 33 bilateral) for OTR (subjective visual vertical [SVV], ocular torsion, skew deviation) to localize causative brainstem lesions in MRI. RESULTS: Unilateral INO was accompanied by at least one component of OTR: SVV tilt in 96%, ocular torsion in 79%, and skew deviation in 50%. All components were directed to the contralesional side. Contralateral OTR occurred in 89% of patients with one-and-a-half syndrome. Only 9% of patients with bilateral INO exhibited OTR. MRI showed distinct lesions in 68%, which almost exclusively projected onto the pontomesencephalic medial longitudinal fascicle (96%). Follow-up measurements revealed SVV and ocular torsion normalized faster than the adduction deficit in INO. CONCLUSIONS: First, unilateral internuclear ophthalmoplegia (INO) is regularly associated with contraversive ocular tilt reaction (OTR): INO plus. Thus, graviceptive pathways join the medial longitudinal fascicle after crossing between the vestibular and abducens nuclei. Second, the different time course and degree of recovery of OTR components and INO signs can be explained by the hypothesis that vestibular tone imbalance is compensated by central vestibular adaptation mechanisms (probably driven mainly by cerebellar-vestibular projections), whereas impaired adduction is less susceptible to compensation according to Hering's law and can only be overcome by lesion repair. Third, bilateral INO is seldom associated with OTR, confirming that bilateral impairment of graviceptive pathways does not cause imbalance in roll plane.

[Late onset Huntington's disease - a differential diagnosis of Alzheimer's disease]. / Chorea Huntington mit später Manifestation als Differenzialdiagnose der Alzheimer-Krankheit.

A 66-year-old patient was admitted to our memory clinic for diagnostic evaluation of potential Alzheimer's disease (AD). Her family reported progressive disturbances of memory, irritability, fidgetiness, and abrupt movements of the extremities and the head for the last 3 to 4 years. Family history was positive for progressive cognitive deterioration associated with movement disturbances beginning at the age of 65 years. Examination revealed mild dementia as well as involuntary choreatiform movements of the extremities and the head. Genetic testing showed an expanded CAG repeat of 41 in the Huntington's disease (HD) gene leading to the diagnosis of HD with mild dementia. Because the age of onset of HD is typically between 35 to 50 years, HD is rarely considered as a differential diagnosis for dementia in elderly patients. This case shows the relevance of an accurate differential diagnosis of cognitive disturbances in order to detect rare causes of dementia.

HSV-1 not only in human vestibular ganglia but also in the vestibular labyrinth.

Reactivation of herpes simplex virus type 1 (HSV-1) in the vestibular ganglion (VG) is the suspected cause of vestibular neuritis (VN). Recent studies reported the presence of HSV-1 DNA not only in human VGs but also in vestibular nuclei, a finding that indicates the possibility of viral migration to the human vestibular labyrinth. Distribution of HSV-1 DNA was determined in geniculate ganglia, VGs, semicircular canals, and macula organs of 21 randomly obtained human temporal bones by nested PCR. Viral DNA was detected in 48% of the labyrinths, 62% of the VGs, and 57% of the geniculate ganglia. The potential significance of this finding is twofold: (1) Inflammation in VN could also involve the labyrinth and thereby cause acute unilateral vestibular deafferentation. (2) As benign paroxysmal positional vertigo often occurs in patients who have had VN, it could also be a sequel of viral labyrinthitis.

Exercise and drug therapy alter recovery from labyrinth lesion in humans.

Acute unilateral vestibular failure is characterized by rotatory vertigo, horizontal-rotatory nystagmus, and postural imbalance, all of which last from days to weeks. These signs and symptoms are caused by a vestibular tone imbalance between the two labyrinths. Recovery results from a combination of peripheral restoration of labyrinthine function (usually incomplete) and central vestibular compensation (CVC) of the vestibular tone imbalance. Acute unilateral failure is most often caused by vestibular neuritis, which is most likely due to the reactivation of a latent HSV-1 infection. Therefore, therapeutic strategies to improve the outcome of VN are theoretically based on two principles: (a) vestibular exercises and drugs to improve CVC and (b) drug treatment of the assumed viral inflammation. The following conclusions can be drawn from studies in animals and/or humans: (1) There is strong evidence that vestibular exercises may improve vestibulo-spinal compensation. These exercises should begin as early as possible after symptom onset. Moreover, slower exercises are likely to be more effective than faster exercises because slower ones seem to depend more on the vestibular system. (2) Despite extensive data from animal experiments indicating that drugs have a favorable effect on CVC, this has not been clinically proven and thus cannot be recommended yet. (3) Preliminary results of an interim analysis from an ongoing randomized, prospective study showed that methylprednisolone (plus an antiviral agent?) may be useful for improving peripheral vestibular function in vestibular neuritis.

Prevalence of HSV-1 LAT in human trigeminal, geniculate, and vestibular ganglia and its implication for cranial nerve syndromes.

Herpes simplex virus type 1 (HSV-1) enters sensory neurons and can remain latent there until reactivation. During latency restricted HSV-1 gene expression takes place in the form of latency-associated transcripts (LAT). LAT has been demonstrated to be important not only for latency but also for reactivation, which may cause cranial nerve disorders. Tissue sections of the trigeminal ganglia (TG), geniculate ganglia (GG), and the vestibular ganglia (VG) from seven subjects were examined for the presence of LAT using the in situ hybridization technique. LAT was found on both sides in allTG (100%), on both sides of five subjects (70%) in the GG, and in none of the VG. Using a second more sensitive detection method (RT-PCR), we found LAT in the VG of seven of ten other persons (70%). This is the first study to demonstrate viral latency in the VG, a finding that supports the hypothesis that vestibular neuritis is caused by HSV-1 reactivation. The distribution of LAT in the cranial nerve ganglia indicates that primary infection occurs in the TG and GG and subsequently spreads along the faciovestibular anastomosis to the VG.

Acute vestibulopathy.

Acute vestibulopathy is characterized by the acute or subacute onset of vertigo, dizziness or imbalance with or without ocular motor, sensory, postural or autonomic symptoms and signs, and can last for seconds to up to several days. Acute vestibular lesions may result from a hypofunction or from pathological excitation of various peripheral or central vestibular structures (labyrinth, vestibular nerve, vestibular nuclei, cerebellum or ascending pathways to the thalamus and the cortex). This update focuses on new aspects of the aetiology, pathophysiology, epidemiology, and treatment of (i) acute peripheral disorders (benign paroxysmal positioning vertigo, vestibular neuritis, Menière's disease, perilymph fistula, especially 'superior canal dehiscence syndrome', vestibular paroxysmia); and (ii) acute central vestibular disorders (especially 'vestibular migraine'). Finally, the clinical relevance of recent diagnostic tools (three-dimensional analysis of eye movement, imaging techniques) is discussed.

Detection of herpes simplex virus type 1 in human vestibular nuclei.

The distribution of herpes simplex virus type 1 (HSV-1) in human geniculate, vestibular ganglia, and vestibular nuclei was determined in 10 human temporal bones and brainstems of five individuals by PCR. HSV-1 was found in 3 of 10 of each ganglia and vestibular nuclei. The various patterns of HSV-1 infection of vestibular structures are compatible with virus migration from the vestibular ganglia to the vestibular nuclei and from the ipsilateral to the contralateral vestibular nucleus via commissural fibers.

Rotational vertebral artery occlusion syndrome with vertigo due to "labyrinthine excitation".

Leftward head rotations in a patient with a rotational vertebral artery occlusion syndrome elicited recurrent uniform attacks of severe rotatory vertigo and tinnitus in the right ear. These attacks were accompanied by a mixed clockwise torsional downbeat nystagmus with a horizontal component toward the right. A transient ischemia of the right labyrinth probably induced the attacks and led to a combined transient excitation of the right anterior and horizontal semicircular canals as well as the cochlea.

Subjective straight-ahead during neck muscle vibration: effects of ageing.

The subjective visual straight-ahead (SVA) was measured psychophysically before and during unilateral vibration of the posterior neck muscles in order to determine the particular contribution of neck muscle spindles to the perception of body orientation during ageing. We found a symmetrical increase of the vibration-induced displacement of the SVA with advancing age (R = +0.73, p < 0.01, n = 60) in 30 healthy subjects of different ages (range 20-81 years). These data indicate the cervical proprioceptive contribution to multisensory body orientation increases with ageing. One possible interpretation is that the sensorial weight of proprioception increases as the peripheral vestibular input decreases with advancing age, thereby substituting for the lack of vestibular function.

Distribution of herpes simplex virus type 1 in human geniculate and vestibular ganglia: implications for vestibular neuritis.

Vestibular neuritis is a common cause of partial unilateral vestibular paralysis, which usually spares posterior semicircular canal function. The cause is assumed to be a viral reactivation of latent herpes simplex virus type 1 (HSV-1) in human vestibular ganglia. The existence of an anastomosis between the intermediate nerve and the superior vestibular nerve suggests the question of whether selective affliction of the superior vestibular nerve is the result of migration of HSV-1 from the geniculate ganglion along this faciovestibular anastomosis. We determined the distribution of HSV-1 among geniculate ganglia, vestibular ganglia, and within Scarpa's ganglion by examining 35 human temporal bones by polymerase chain reaction. HSV-1 was found in 66% of geniculate ganglia and 60% of vestibular ganglia; all examined parts of vestibular ganglia were almost equally HSV-1 infected. Our data provided no support for viral migration along this anastomosis or for a preferential latency of HSV-1 in the superior vestibular nerve. We suggest that the common double innervation of the posterior ampulla by two nerves running in two separate bony canals could offer an alternative explanation for the regular sparing of posterior canal function in vestibular neuritis.

Cogan's syndrome: clinical significance of antibodies against the inner ear and cornea.

The aim of this study was to evaluate the pathological significance of antibodies against cornea and inner ear tissue in the development of audiovestibular and ocular symptoms in patients with Cogan's syndrome (CS). We analysed the serum of 5 CS patients for binding of IgM and IgG to fresh cryosections of rat labyrinth (semicircular canals, ampulla, utricle, saccule) and cornea by indirect immunofluorescence (IF). The predominant pattern of anti-corneal IgM was staining of the superficial cell layer of the non-keratinizing squamous epithelium. IgM against cornea was found in 3 patients, all of whom had bilateral inflammatory eye signs at the start of the disease. However, IgM was also detected in the chronic stage of the disease when no clinical signs of eye involvement were apparent. The study includes the first follow-up examination of anti-corneal IgM and IgG antibodies during a complete episode of active CS. During the first episode of CS in 1 patient, anti-corneal IgM became detectable 1 week after the onset of interstitial keratitis and 3 weeks after the onset of audiovestibular symptoms. It increased over several weeks and then fell to very low levels. However, at no time was anti-corneal IgG found. In the course of follow-up examinations, the serum of 4 patients intermittently contained low titre IgG antibodies against inner ear labyrinthine tissue, but without any clear correlation with the active stages of CS. In addition, high-resolution MRI (HR-MRI) of the inner ear was performed in the acute and chronic stages of CS to evaluate the activity of CS. In the acute stage, HR-MRI revealed abnormal MRI signals in the vestibule, semicircular canals, vestibular nerve, or cochlea. In the chronic stage, patients showed narrowing or occlusion of semicircular canals and the cochlea on the 3D-CISS images, but no high signal lesions (T1) and no enhancement. Antibodies against cornea or labyrinthine tissue were not consistently detected in CS and the level of organ-specific antibodies did not correlate with the activity of the disease.

[Progressive multifocal leukoencephalopathy as a result of immunosuppressive therapy]. / Progressive Multifokale Leukenzephalopathie als Folge immunsuppressiver Behandlung.

HISTORY AND ADMISSION FINDINGS: A 62-year-old woman developed paresis in her right arm within several weeks. She was being treated with methylprednisolone (4 mg daily) and chlorambucil (2 mg every other day) for systemic lupus erythematodes (SLE), which was now in remission. Neurological examination on admission revealed a right flaccid hemiparesis, predominantly of the right arm. The physical examination was otherwise unremarkable. INVESTIGATIONS: Magnetic resonance imaging (MRI) (T2 weighted) showed hyperintense changes in the subcortical medullary layer of the left precentral gyrus without perifocal oedema or abnormal contrast medium uptake, which argued against progressive cerebral ischaemia or tumour. Blood and cerebrospinal fluid (CSF) showed no abnormalities except leukopenia and a raised antinuclear antibody titre. Progressive paralysis of the right side of the body after 2 years of immunosuppressive treatment, the MRI findings and an essentially normal CSE suggested progressive multifocal leucoencephalopathy (PML), confirmed by polymerase chain reaction (PCR) demonstrating JC-virus DNA in serum and CSF. TREATMENT AND COURSE: As a result of the CNS infection with papovavirus JC, an opportunistic infection of the central nervous system, which is usually fatal, occurred. The cerebral changes spread within a few weeks, despite of the immunosuppressive drugs having been discontinued. The pareses progressed further and a marked personality disorder of organic origin ensued. CONCLUSION: While efficacious immunosuppressive drugs against autoimmune disease are available, their use risks the occurrence of life-threatening opportunistic infections.

Sympathetic contralateral vestibulopathy after unilateral zoster oticus.

A unique case of initially right sided varicella zoster induced Ramsay-Hunt syndrome with complete vestibular loss is reported. The patient subsequently developed deficits of the left vestibule 5 months later. An autoimmune pathogenesis of the left vestibular failure rather than bilateral varicella zoster infection was suggested by the following data: (1) no evidence of vesicular eruptions on the left auricle and the virtual absence of antiviral antibodies after onset of bilateral vestibulopathy; (2) prompt response of the left vestibule to immunosuppressive therapy with corticosteroids; and (3) presence of atypical nervous tissue specific autoantibodies against a 45 kDa protein.

High resolution Gd-DTPA MR imaging of the inner ear in 60 patients with idiopathic vestibular neuritis: no evidence for contrast enhancement of the labyrinth or vestibular nerve.

Sixty patients with acute idiopathic vestibular neuritis (confirmed by clinical examination and caloric irrigation) were evaluated in a prospective study by high resolution magnetic resonance imaging (hr-MRI) between days 3 and 30 after onset of symptoms. We used a 1.5 Tesla imager with an axial and coronal T1-weighted 2D-fast low angle shot-, T2-weighted turbo spin echo-, and an axial T2-weighted 3D-constructive interference in steady-state sequence for MRI. None of the patients' MRIs exhibited contrast enhancement of the labyrinth, vestibulocochlear nerve, or vestibular ganglion, even when high doses of gadolinium (0.2 mmol/kg) were used. In contrast, several previous studies demonstrated contrast enhancement of the vestibulocochlear nerve/labyrinth in herpes zoster oticus, labyrinthitis, and Cogan's syndrome or of the facial nerve in Bell's palsy. On the basis of our MRI findings, we speculate that idiopathic vestibular neuritis is neither a viral infection directly affecting the nerve (such as herpes zoster) nor a labyrinthitis. An autoimmunological disease of the labyrinth, which should involve only the anterior and horizontal semicircular canals, is also unlikely. A subacute reactivation of a latent viral infection--as discussed for Bell's palsy--is compatible with our MRI findings. The observed differences between contrast enhancement of the facial nerve in Bell's palsy and the vestibulocochlear nerve in vestibular neuritis may be due to their dissimilar anatomy: contrary to the vestibular nerve, the facial nerve has very prominent circumneural arteriovenous structures. Hyperemia within these vascular structures may cause the contrast enhancement seen in Bell's palsy.

Alternating episodes of vestibular nerve excitation and failure.

Recurrent episodes of oscillopsia, rotational vertigo, and postural imbalance were elicited and modulated by changing the horizontal head positions of a patient with an arachnoid cyst in the right cerebellopontine angle that distorted the vestibulocochlear nerve. Oculomotor analysis revealed two different types of attacks depending on the particular head position: 1) episodes of vestibular hypofunction (minutes to several hours) with normal head position and 2) paroxysmal vestibular excitation (seconds) with head rotation to the left. The most likely cause is a transition from conduction block to ectopic discharges, which occurs when various peripheral nerves are compressed. One week after resection of the cyst and decompression of the eighth cranial nerve the patient was symptom free, and the electronystagmogram was normal.