Isolated cranial nerve palsies due to brainstem lesions.

Isolated cranial nerve palsies are often attributed to lesions of the respective nerves along their extraaxial courses. There are a significant number of reports of individual patients with cranial nerve palsies, mostly of the 3rd and 6th nerves, as the sole manifestation of brainstem lesions proven by magnetic resonance imaging (MRI) or computer-assisted tomography (CT). An intraaxial basis may still be underestimated if based on MRI only, as electrophysiological abnormalities indicating brainstem lesions (masseter reflex, blink reflex, DC electrooculography) may be independent from MRI-documented morphological lesions. This article reviews the evidence that ischemic and demyelinating brainstem lesions are an important and underestimated cause of clinically isolated cranial nerve palsies. Especially in middle-aged and elderly people with 3rd and 6th nerve palsies, small pontine and mesencephalic infarctions seem to be more frequent than small-vessel ischemic infarctions of the extraaxial nerves.     

Cerebrovascular brainstem diseases with isolated cranial nerve palsies

There is a significant number of individual patients with cranial nerve palsies as the sole manifestation of MRI- and, less frequently, CT-documented small brainstem infarctions or hemorrhages. The 3rd and 6th nerves are most commonly involved and, less frequently, the 4th, 5th, 7th, and 8th nerves. An intra-axial basis for such lesions may be underestimated if the diagnosis is based solely on MRI. The electrophysiologic abnormalities indicating brainstem lesions may be independent of MRI-documented morphological lesions. This paper reviews the literature on cerebrovascular brainstem diseases manifesting as isolated cranial nerve palsies. It supports the concept that small pontine and mesencephalic infarctions are the main cause of non-traumatic cranial nerve palsies in the middle-aged and elderly population. Microvascular infarction of the respective extra-axial cranial nerve segments seem to be less important.     

Sixth nerve palsy as a presenting sign of intracranial plasmacytoma and multiple myeloma.

Multiple myeloma and plasmacytoma are rare causes of mass lesions at the skull base and cavernous sinus. Sixth nerve palsy, in isolation or in combination with other cranial neuropathies, may occur rarely as the initial presenting feature of multiple myeloma. We report the neuro-ophthalmologic, radiologic, and pathologic findings for two patients who developed sixth nerve palsies as an initial manifestation of intracranial plasmacytoma and multiple myeloma. One patient presented with an isolated sixth nerve palsy in the setting of multiple vasculopathic risk factors. Treatable skull base lesions, including plasmacytoma and multiple myeloma, must be considered in patients with sixth nerve palsies, especially among those who demonstrate a progressive course or multiple cranial neuropathies.     

Unilateral multiple cranial nerve palsies mimicking Garcin syndrome as an atypical symptom of brainstem encephalitis: a case report]

We report a 56-year-old Japanese man who was admitted because of dysphagia and left side facial dysesthesia. On admission, his general conditions were unremarkable. Neurological examination revealed that he was alert and well oriented. He exhibited left-side cranial nerve involvement such as the trigeminal(sensory and motor), glossopharyngeal and potential vagal nerve palsy. He exhibited neither long-tract signs, such as motor weakness, sensory disturbance in his exremities and pathological reflex, nor ataxia. By a few days after admission, his symptoms had worsened. Vertigo and diplopia appeared, and his consciousness level became drowsy. Bilateral third and sixth nerves, left fourth, fifth, eighth, ninth and tenth nerves were involved. Results of laboratory tests and CSF studies were within normal. Results of examination of the skull base X-ray and MRIs of the brain were normal. Administration of corticosteroid and intravenous administration of a high dose of gamma-globulin were not effective. His symptoms gradually recovered three months after admission. Based on clinical symptoms and results of physiological examination, i.e., an involvement of his consciousness and abnormal findings in blink reflex test that suggest involvement of the brainstem, he was diagnosed as having brainstem encephalitis. Although the exact pathophysiological mechanisms were unclear, it is clinically important to note that an atypical brainstem encephalitis may present a subacute progressive appearance of unilateral multiple cranial nerve palsies mimicking Garcin syndrome.     

Seventh nerve palsies may be the only clinical sign of small pontine infarctions in diabetic and hypertensive patients

Backgroud: Small brainstem infarctions are increasingly recognized as a cause of isolated ocular motor and vestibular nerve palsies in diabetic and/or hypertensive patients. This raises the question whether there are also isolated 7^th nerve palsies due to pontine infarctions in patients with such risk factors for the development of cerebrovascular diseases. Methods: Over an 11-year-period, we retrospectively identified 10 diabetic and/or hypertensive patients with isolated 7^th nerve palsies and electrophysiological abnormalities indicating pontine dysfunction. All patients had examinations of masseter and blink reflexes, brainstem auditory evoked potentials, direct current electro-oculography including bithermal caloric testing, and T1- and T2-weighted MRI (slice thickness: 4–7 mm). Results: Electrophysiological abnormalities on the side of the 7^th nerve palsy included delayed masseter reflex latencies (4 patients), slowed abduction saccades (4 patients), vestibular paresis (2 patients), and abnormal following eye movements (2 patients). Electrophysiological abnormalities were always improved or normalized at re-examination, which was always associated with clinical improvement. MRI revealed an ipsilateral pontine infarction in 2 patients. Another 2 had bilateral hyperintense intrapontine lesions, and one an ipsilateral cerebellar infarction. Conclusions: Simultaneous improvement or recovery of abnormal clinical and electrophysiological findings strongly indicated that both were caused by the same actual pontine lesions. A 7^th nerve palsy may be the only clinical sign of a pontine infarction in diabetic and/or hypertensive patients. Such mechanism may be underestimated if based on MRI only. Received: 24 January 2002, Received in revised form: 22 May 2002, Accepted: 4 June 2002 Correspondence to Frank Th?mke, MD     

Isolated superior oblique palsies with brainstem lesions.

Isolated unilateral superior oblique palsies resulting from brainstem lesions occurred in three patients. MRI documented contralateral tegmental lesions of the trochlear nucleus and adjacent intraaxial trochlear nerve. Lacunar infarct was the cause in two patients and a small hemorrhage in a third.     

Magnetic resonance imaging of third cranial nerve palsy and trigeminal sensory loss caused by herpes zoster.

A 44-year-old man with right-sided herpes zoster ophthalmicus (HZO) developed ipsilateral third and sixth cranial nerve palsies and first-division trigeminal (fifth cranial nerve) sensory loss. MRI revealed contrast enhancement of the cisternal and cavernous portions of the third cranial nerve and high signal on a FLAIR sequence within the ipsilateral medulla at the presumed location of the trigeminal nucleus and tract. To our knowledge, this is the first report of the combination of these imaging findings in HZO.     

Isolated cranial nerve palsies in multiple sclerosis

Data on patients with multiple sclerosis and cranial nerve involvement as a presenting sign or a sign of disease exacerbation were retrospectively analyzed. Isolated cranial nerve involvement was present in 10.4% out of 483 patients, either as a presenting symptom (7.3%) or a symptom of disease relapse (3.1%). Trigeminal nerve was most frequently involved, followed by facial, abducens, oculomotor and cochlear nerves. Only 54% of patients had brainstem MRI lesion that could explain the symptoms. As multiple sclerosis is a disease characterized by multiple neurological symptoms, while early diagnosis and therapy are critical for the prognosis and course of the disease, the diagnosis of multiple sclerosis should be considered in young adults with cranial nerve involvement.     

Isolated sixth nerve palsy: an uncommon presenting sign of multiple sclerosis

We describe three patients in whom an isolated sixth nerve palsy was the only clinical symptom or sign of multiple sclerosis (MS). Data were collected prospectively over 6 years on these three patients, who showe no other signs of brainstem dysfunction or prior symptoms; in addition. Retrospective analysis of all patients with MS and all patients with sixth nerve palsy referred to a neuro-ophthalmology service between 1982 and 1998 showed isolated sixth nerve palsy to be the presenting sign of MS in only 0.5% of these patients. MS was the cause of isolated sixth nerve palsy in 0.8% of all patients and in 1.6% of those aged 18–50 years. Although it has been previously suggested that sixth nerve palsy is an ot uncommon presenting sign of MS, our results suggest it is rare. Received: 15 November 1999/Received in revised form: 15 March 2000/Accepted: 26 April 2000     

CNS involvement in hereditary neuropathy with pressure palsies (HNPP)

We assessed seven patients with hereditary neuropathy with liability to pressure palsies (HNPP) with 16 electrophysiological tests and cranial MRI for CNS abnormalities. Mean latencies differed between patients with HNPP and controls for the blink reflex, the jaw-opening reflex, and acoustic evoked potentials. MRI abnormalities were observed in four patients. Our study suggests subclinical but functionally relevant CNS myelin damage in HNPP.     

Electrophysiological brainstem testing in the diagnosis of reversible brainstem ischemia

The aim of this study was to evaluate the sensitivity of multimodal electrophysiological brainstem testing in the diagnosis of clinically suspected reversible ischemic deficits of the brainstem compared with diffusion weighted MR imaging. We investigated 158 consecutive patients presenting with signs of acute brainstem dysfunction. Serial electrophysiological brainstem tests including masseter reflex, blink reflex, masseter inhibitory reflex, AEP, MEP, EOG and the oculoauricular phenomenon were applied. In 14 of the 158 patients neurological deficits resolved in less than 24 hours, which was suggestive of a transitory ischemic attack (TIA), 19 patients had brainstem signs for more than 24 hours but less than 1 week, suggestive of a reversible ischemic neurological deficit (RIND). Electrophysiological data indicated acute functional brainstem lesions in 54,5 % of patients with transient clinical brainstem impairment. Lesion detection rate was significantly higher when combining electrophysiological data and MRI (60,4 %) than using acute brainstem abnormalities in diffusion weighted MRI alone (39,4 %). We conclude that diffusion weighted MRI and electrophysiological brainstem testing are complimentary sensitive indicators of acute brainstem lesions in patients with reversible neurological deficits. Correct identification of brainstem ischemia influences the therapeutic regimen and may improve patient outcome. Received: 5 November 2001 Received in revised form: 28 January 2002 Accepted: 1 February 2002     

Isolated superior oblique palsies with electrophysiologically documented brainstem lesions

Over a 13.5-year period, we observed 10 patients with isolated superior oblique palsies in whom electrophysiological abnormalities indicated brainstem lesions. In 7 patients unilateral masseter reflex abnormalities were seen, and were located on the side of the superior oblique palsy in 2 patients and on the opposite side in 5 patients. Two patients had slowed gain of following eye movements to the side contralateral to the superior oblique palsy. Slowed adduction saccades in the eye contralateral to the superior oblique palsy were seen in 1 patient. Clinical improvement was frequently (in 7 of 10 patients) associated with improvement or normalization of electrophysiologic findings. Magnetic resonance imaging (MRI) was normal, showing no evidence of brainstem lesions in 6 patients. Unilateral superior oblique palsy may be the only clinical sign of a brainstem lesion. Although such a cause may be underdiagnosed if based on MRI-documented lesions only, it remains a rare condition.     

A clinicopathological study of a patient with anti-Hu-associated paraneoplastic sensory neuronopathy with multiple cranial nerve palsies

Only a few cases of paraneoplastic neurologic syndrome with multiple cranial palsies have been reported. This is the case report of a patient with small-cell lung cancer and a high titer of anti-Hu antibodies who developed a tonic left pupil and multiple cranial nerve palsies, including palsies of the left fifth through tenth nerves and both twelfth nerves, as in Garcin syndrome showing at least more than seven ipsilateral cranial nerve palsies, in the course of paraneoplastic sensory neuronopathy (PSN). Pathologic examination revealed no metastasis or direct invasion of malignancy with gliosis and perivascular inflammation throughout the brainstem, indicating paraneoplastic encephalomyelitis (PEM). The numbers of EBM11+ cells (probably reactive microglia), CD8+ cells, and CD4+ cells increased. Intracellular adhesion molecule-1 and lymphocyte function associated molecule-1 were expressed intensely on the endothelia of microvessels and were found to have infiltrated mononuclear cells around microvessels in the brainstem. Multiple cranial nerve palsies and their effects including the tonic pupil are likely due to the paraneoplastic effect of the primary systemic malignancy.     

Isolated monolateral neurosensory hearing loss as a rare sign of neuroborreliosis

Abstract. Lyme disease, or borreliosis, is a zoonosis transmitted by Borrelia burgdorferi which also involves the central nervous system (CNS), in 15% of affected individuals, with the occurrence of aseptic meningitis, fluctuating meningoencephalitis, or neuropathy of cranial and peripheral nerves. Encephalopathy with white matter lesions revealed by magnetic resonance imaging (MRI) scans in late, persistent stages of Lyme disease has been described. In this report, we describe a patient with few clinical manifestations involving exclusively the eighth cranial nerve, monolaterally and diffuse bilateral alterations of the white matter, particularly in the subcortical periventricular regions at cerebral MRI. This single patient study shows that the search for antibodies against Borrelia burgdoferi should always be performed when we face a leukoencephalopathy of unknown origin. An isolated lesion of the eighth cranial nerve can be the only neurologic sign in patients with leukoencephalopathy complicating Lyme disease.     

Anti-hu paraneoplastic syndrome presenting as bilateral sixth cranial nerve palsies.

A 62-year-old woman presented with diplopia caused by bilateral sixth cranial nerve palsies. Two weeks later, she had bulbar weakness and ataxia. Brain magnetic resonance imaging showed non-specific abnormalities and spinal fluid was acellular but contained an elevated protein and oligoclonal bands. A paraneoplastic screen showed anti-Hu antibodies. Her clinical condition improved with immunoglobulin and systemic corticosteroid treatment. Breast cancer was diagnosed 21 months later by mammography but there were no metastases detected. Four and half years after the onset of her diplopia, she died of diffuse metastatic breast cancer. This is the first reported case of anti-Hu paraneoplastic brain stem encephalitis presenting with sixth cranial nerve palsies.     

A case of AIDS associated cryptococcal meningitis with multiple cranial nerve neuropathies

Cryptococcal meningitis is a common opportunistic infection among patients with AIDS. Cranial nerve neuropathies are well-known complications that occur due to increased intracranial pressure and inflammation of cranial nerves in such patients but have not been previously reported to involve more than four cranial nerves simultaneously. Our patient had involvement of five cranial nerves resulting in the complete loss of vision and hearing as well palsies of the third, sixth and seventh cranial nerves. He was treated with multiple antifungal medications. Repeated high volume lumbar punctures and Ommaya reservoir were used to lower intracranial pressure. At the time of discharge the patient had complete recovery of the functions of third, sixth and seventh cranial nerves bilaterally and partial recovery of hearing and vision.     

Sixth and twelfth cranial nerve palsies following Basal skull fracture involving clivus and occipital condyle

Oblique basal skull fractures resulting from lateral crushing injuries involving both clivus and occipital condyle are rare due to their deep locations. Furthermore, these fractures may present clinically with multiple cranial nerve injuries because neural exit routes are restricted in this intricate region. The authors present an interesting case of basal skull fractures involving the clivus and occipital condyle and presenting with sixth and contralateral twelfth cranial nerve deficits. Clinico-anatomic correlations and the courses of cranial nerve deficits are reiterated. To the authors' knowledge, no other report has been previously issued on concomitant sixth and contralateral twelfth cranial nerve palsies following closed head injury.     

MRI findings in Möbius syndrome: correlation with clinical features

The authors studied the MRI findings of three patients with M?bius syndrome. M?bius syndrome is a rare congenital disorder characterized by complete or partial facial diplegia accompanied by other cranial nerve palsies. MRI demonstrated brainstem hypoplasia with straightening of the fourth ventricle floor, indicating an absence of the facial colliculus. These MRI features suggest the diagnosis of M?bius syndrome and correlate with the clinical and neurophysiologic findings.     

Asymptomatic spinal cord lesions in clinically isolated optic nerve, brain stem, and spinal cord syndromes suggestive of demyelination

OBJECTIVES—Conventional T2 weighted MRI studieshave highlighted the fact that the presence of clinically silent brainlesions increases the risk of developing clinically definite multiplesclerosis after an isolated syndrome of the optic nerve, brain stem, or spinal cord. The objectives of the present study are: (1) to show whether or not these patients also have asymptomatic abnormalities ofthe spinal cord, and (2) to recruit a new cohort of such patients usinghigh resolution MRI of both brain and spinal cord.
METHODS—The brain was imaged in the axial planewith 3 mm thick contiguous slices using a proton density and T2weighted fast spin echo (FSE) sequence; a T1 weighted sequence afterthe injection of gadolinium-DTPA; and a fast fluid attenuated inversionrecovery (fFLAIR) sequence. The spinal cord was imaged in the sagittal plane with 3 mm thick slices using a T2 weighted FSE and a T1 weightedgadolinium enhanced sequence.
RESULTS—Thirty three patients, meanage 31 (16-46) were recruited. There were 14 men and 19 women. BrainMRI was abnormal in 22 (67%); no patient was seen with abnormalitieson only one or other sequence. Six patients (18%)displayed one or more gadolinium enhancing lesions on brain MRI. In thespinal cord, nine (27%) patients displayed one or more clinicallysilent lesions on FSE. Two patients showed one and two gadoliniumenhancing lesions in the spinal cord respectively.
CONCLUSION—This high incidence of spinal cordlesions emphasises that asymptomatic demyelinating lesions may alsoinvolve clinically eloquent pathways. Follow up studies are required todetermine their prognostic importance.

     

Solitary brainstem metastasis

Progressive cranial nerve palsies and long-tract signs without increased intracranial pressure developed in three patients. All had a history of cancer, but two had been in remission for more than 5 years and were thought to be cured of the malignancy. The patients were treated with cranial irradiation and glucocorticoids, following which one patient made a dramatic neurologic recovery. In each case, postmortem examination showed a brainstem metastasis with no metastatic lesions elsewhere in the nervous system. An occult metastasis should be considered when signs or symptoms suggest brainstem tumor in an adult.