Eun Hye Oh

Intravenous tissue plasminogen activator in acute branch atheromatous disease: Does it prevent early neurological deterioration?

Early neurological deterioration (END) and poor outcome frequently occur in lenticulostriate artery (LSA) infarction due to branch atheromatous disease (BAD). We evaluate whether the tissue plasminogen activator (tPA) can prevent END and improve the outcome by comparing with anti-platelet treatment in LSA infarction due to BAD. We enrolled the patients with LSA infarction due to BAD who arrived at the hospital within 24h from onset, and divided those into two groups by whether tPA was given or not. END and good outcome (modified Rankin score: 0-1) at 3months were examined between two groups. Consecutive 35 patients of LSA infarction due to BAD enrolled in this study. Nine patients were given tPA (tPA group) and 26 patients antiplatelets only (non-tPA group). Patients in tPA group showed no symptomatic hemorrhage. END occurred in 68.6% (24/35) of all patients, 66.7% (6/9) of tPA group and 69.2% (18/26) of non-tPA group (p=0.886). The proportion of good outcome at 3months were 25.7% in all patients, 22.2% (2/9) in tPA group and 26.9% (7/26) in non-tPA (p=0.781). tPA did not adequately prevent END, and did not show better outcome in LSA infarction due to BAD compared with antiplatelet therapy only. More effective treatment strategies are needed for prevention of END and favourable outcome in BAD.

Persistent geotropic positional nystagmus in unilateral cerebellar lesions

Objective To determine the prevalence of central lesions in persistent geotropic positional nystagmus, and characteristics and anatomical substrates of the nystagmus in cerebellar lesions. Methods We prospectively recruited 58 patients with persistent geotropic positional nystagmus at the Dizziness Clinic of Pusan National University Hospital. Seven patients with unilateral cerebellar lesions were subjected to analysis of clinical characteristics, oculographic data, and MRI lesions. For comparison, we studied 37 cases of peripheral persistent geotropic positional nystagmus. Results The prevalence of central lesions in persistent geotropic positional nystagmus was 12% (7/58). Persistent geotropic positional nystagmus in cerebellar lesions was mostly asymmetrical. Horizontal nystagmus changed in direction during the bow-and-lean test with null positions. All patients showed impaired horizontal smooth pursuit bilaterally, and 3 of them also had positional downbeat nystagmus. The peak intensity and asymmetry of persistent geotropic positional nystagmus did not differ between central and peripheral groups (p > 0.05), while there was a difference in the maxima. Lesion overlays revealed that damage to the cerebellar tonsil was responsible for the generation of persistent geotropic positional nystagmus. Conclusion Although persistent geotropic positional nystagmus in cerebellar lesions shares the characteristics of nystagmus measures with peripheral cases, accompanying central oculomotor signs can aid in differentiation. In tonsillar lesions, compensatory rotational feedback due to erroneous estimation of the direction of gravity may generate constant horizontal geotropic positional nystagmus.

Atypical clinical manifestations of Miller Fisher syndrome

Miller Fisher syndrome (MFS) is characterized by a clinical triad of ophthalmoplegia, ataxia, and areflexia, and is closely associated with serum anti-GQ1b antibody. Although the clinical triad is the cardinal diagnostic clue, a variety of other symptoms and signs beyond the triad have been reported. To elucidate the frequency and characteristics of atypical clinical manifestations of MFS, we recruited 38 patients with MFS and evaluated the symptoms or signs beyond the classic triad. Eleven (29%) of 38 patients had atypical clinical manifestations of MFS such as headache (n = 6), delayed facial palsy (n = 3), divergence insufficiency (n = 2), and taste impairment (n = 2). Headache was localized to the periorbital (n = 3), temporal (n = 2), or whole (n = 1) area. Only one of them showed bilateral papilledema and an elevated opening pressure in cerebrospinal fluid analysis. Delayed facial palsy developed after the other signs have reached nadir (n = 1) or started to improve (n = 2), and did not follow a pattern of descending paralysis with other cranial neuropathies. Two patients showed divergence insufficiency without external ophthalmoplegia, and another two had taste impairment over the entire tongue without the other signs of facial and glossopharyngeal nerve involvements. Our study shows that approximately 30% of MFS patients can have atypical clinical manifestations beyond the classic triad. These results reflect the broad clinical spectrum of MFS, and might be associated with the presence of additional antiganglioside antibodies besides anti-GQ1b in patients with MFS.

Early MRI-negative posterior circulation stroke presenting as acute dizziness

The aim of this study was to determine the frequency, clinical and radiological features, and efficacy of clinical evaluation and perfusion-weighted imaging (PWI) for the prediction of final stroke in patients with DWI/MRI-negative posterior circulation stroke (PCS) presenting acute dizziness/vertigo. From our comprehensive prospective stroke registry of acute ischemic stroke during a 7-year period, we identified 1846 consecutive patients with PCS, 850 of whom presented with acute dizziness/vertigo. Of these 850 patients, initial DWI-MRI was negative in 35 (4.1%). In these 35 patients, dizziness/vertigo was acute prolonged in 31 and recurrent transient in 4. Focal neurological signs or profound imbalance were present in 16/35 or 18/34, respectively. Spontaneous nystagmus was absent in 21/35; the HINTS protocol (head impulse, nystagmus, and test-of-skew) was not applicable to them. In 12/26 patients, PWI was positive and the same time as DWI was negative. The usual site of lesion was the lateral medulla (n = 18). Twenty-nine patients (83%) had small strokes, while 19 (54%) had large vessel strokes. The sensitivity of systematic clinical evaluation adopting neurological examination, HINTS plus, and assessment of equilibrium was 83%, for prediction of final stroke and 100% when combined with PWI. An integrated approach using systematic neurological and neuro-otological examinations combined with PWI accurately diagnoses PCS presenting with acute dizziness/vertigo. Although most patients with acute vertigo and MRI-negative PCS have small brainstem strokes, about a half have large vessel stroke with greater risk of progression requiring prompt treatment.

Genotype and Phenotype Spectrum of FRMD7-Associated Infantile Nystagmus Syndrome

Purpose We investigate the genotype and phenotype spectrum of FRMD7-associated infantile nystagmus syndrome in Korean probands. Methods A total of 37 patients with infantile nystagmus syndrome were recruited prospectively for genetic analysis. We performed polymerase chain reaction (PCR)-based direct sequencing and haplotype analysis for FRMD7. Detailed ophthalmic examinations and eye movement recordings were compared between FRMD7 and non-FRMD7 groups. Results In 13 (35%) of 37 patients, five different mutations of FRMD7 were detected: start codon mutation c.1A>G, splice site mutation c.162+6T>C, and three missense mutations (c.575A>C, c.722A>G, and c.875T>C). The latter mutation was identified in seven unrelated patients, and always was accompanied with two single nucleotide polymorphisms of exon 12 (rs6637934, rs5977623). Compared to non-FRMD7 groups, a cup-to-disc ratio was significantly decreased in FRMD7 groups (P < 0.001), and a disc-macula distance to disc diameter ratio markedly increased in the FRMD7 group (P = 0.015). Most patients in the FRMD7 group had at least two types of the nystagmus waveforms, and the most common type was unidirectional jerk nystagmus (75%), such as pure jerk and jerk with extended foveation, followed by pendular (25%), bidirectional jerk (19%), and dual jerk (6%) nystagmus. No significant differences were observed between FRMD7 and non-FRMD7 groups in terms of the nystagmus waveform, presence of periodic alternating nystagmus, and mean foveation time. Conclusions We identified five FRMD7 mutations in 35% of our infantile nystagmus syndrome cohort, expanding its mutational spectrum. The missense mutation c.875T>C may be a common mutation arisen from the founder effect in Korea. Optic nerve dysplasia associated with FRMD7 mutations suggests that the abnormal development of afferent visual systems may affect neural circuitry within the oculomotor system.

Fatigable ptosis as an initial presentation of adult-onset Leigh syndrome

A 20-year-old man presented with bilateral fatigable ptosis for 1 month. On examination, there was bilateral incomplete ptosis, which deteriorated during upward gaze and improved at rest (figure, A and B). Tests for myasthenia gravis were all negative. Brain MRI showed symmetric hyperintensities at periaqueductal gray matter on T2- and diffusion-weighted images (figure, C). CSF lactic acid was elevated. Mitochondrial genome test demonstrated a homoplasmic T9176C mutation in the MT-APT6A gene, known as pathogenic mutation of Leigh syndrome.1 In our patient, fatigable ptosis may be ascribed to the dysfunction at centrally located synapse between the nuclear complex of the third nerve and supranuclear pathways.2

Rhythmic pupillary change in Cheyne-Stokes respiration

Cheyne-Stokes respiration is an abnormal pattern of respiration characterized by alternating periods of apnea and hyperpnea with a crescendo-decrescendo pattern [1]. Each episode may last from 30 s to 2 min. It commonly occurs in patients with bilateral cerebral hemispheric lesions or cardiopulmonary dysfunction. The respiratory cycle is associated with the change of serum partial pressure of oxygen and carbon dioxide (pO2 and pCO2). Increased pCO2 during apnea causes excessive compensatory hyperventilation, in turn resulting in decreased pCO2 which causes apnea again. We report a patient showing a rhythmic pupillary change during CheyneStokes respiration.

Patterns and modulations of Pendular nystagmus in a family with hereditary spastic paraplegia

Hereditary spastic paraplegia (HSP) is characterized by progressive spasticity and weakness of the lower extremities. Additional findings include ataxia, extrapyramidal signs, and dementia. Pendular nystagmus (PN) has been reported in some subtypes of HSP caused by PLP1 (SPG2) or paraplegin (SPG7) mutation. To describe the patterns and modulation of PN in HSP, we performed eye movement recording using video-oculography in a Korean family with HSP and PN. The PN was convergent-divergent in the oblique plane with a frequency of 6 to 7Hz and maximum amplitude at about 1.5°. The nystagmus diminished briefly after blinks and horizontal saccades, and decreased during eccentric gaze and convergence. Horizontal saccades shifted the phase of the oscillations. During lateral gazes, the PN increased in the abducting eye, but decreased in the adducting eye. Vibratory stimuli decreased the nystagmus mostly in the left but not in the right eye. No pathogenic mutation was found in the genetic loci known for causing spastic paraplegia by whole-exome sequencing. The unusual features and modulation of PN in our patients with HSP emphasize the role of disconjugate and disjunctive capabilities of the brain in ocular motor control, and exemplify what can go wrong.