Rainer Scheid

Neurologic manifestations of ulcerative colitis

Ulcerative colitis (UC) has traditionally been considered to be an inflammatory disease limited to the colonic mucosa. However, since it has been shown that UC is frequently accompanied by various extraintestinal disorders, there is increasing evidence that UC may also manifest in the nervous system. The following review focuses particularly on these possible manifestations of UC, both in the peripheral (PNS), and in the central nervous system (CNS). A systematic literature search according to the MEDLINE database was performed for this purpose. Although a reliable differentiation may clinically not always be possible, three major pathogenic entities can be differentiated: (i) cerebrovascular disease as a consequence of thrombosis and thromboembolism; (ii) systemic and cerebral vasculitis; (iii) probably immune mediated neuropathy and cerebral demyelination. With the exception of thromboembolism and sensorineural hearing loss, evidence for a causal relationship relies merely on single case reports or retrospective case series. Considering the CNS‐manifestations, similarities between UC‐associated disorders of the white matter and acute disseminated encephalomyelitis (ADEM) are obvious. Epileptic seizures, unspecified encephalopathies and confusional states are most likely epiphenomena that have to be regarded symptomatic rather than as own entities. A prospective study on the neurologic aspects of UC would be very welcome.

Spontaneous Slow Hemodynamic Oscillations are Impaired in Cerebral Microangiopathy

Small-vessel disease or cerebral microangiopathy (CMA) is a common finding in elderly people. It is related to a variety of vascular risk factors and may finally lead to subcortical ischemic vascular dementia. Because vessel stiffness is increased, we hypothesized that slow spontaneous oscillations are reduced in cerebral hemodynamics. Accordingly, we examined spontaneous oscillations in the visual cortex of 13 patients suffering from CMA, and compared them with 14 agematched controls. As an imaging method we applied functional near-infrared spectroscopy, because it is particularly sensitive to the microvasculature. Spontaneous low-frequency oscillations (LFOs) (0.07 to 0.12 Hz) were specifically impaired in CMA in contrast to spontaneous very-low-frequency oscillations (0.01 to 0.05 Hz), which remained unaltered. Vascular reagibility was reduced during visual stimulation. Interestingly, changes were tightly related to neuropsychological deficits, namely executive dysfunction. Vascular alterations had to be attributed mainly to the vascular risk factor arterial hypertension. Further, results suggest that the impairments might be, at least partly, reversed by medical treatment such as angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers. Results indicate that functional near-infrared spectroscopy may detect changes in the microvasculature due to CMA, namely an impairment of spontaneous LFOs, and of vascular reagibility. Hence, CMA accelerates microvascular changes due to aging, leading to impairments of autoregulation.

Neurovascular coupling is impaired in cerebral microangiopathy – An event related Stroop study

Small-vessel disease or cerebral microangiopathy is a common finding in elderly people leading finally to subcortical ischemic vascular dementia. Because cerebral microangiopathy impairs vascular reactivity and affects mainly the frontal lobes, we hypothesized that brain activation decreases during an event-related color-word matching Stroop task. 12 patients suffering from cerebral microangiopathy were compared with 12 age-matched controls. As an imaging method we applied functional near-infrared spectroscopy, because it is particularly sensitive to the microvasculature. The Stroop task led to activations in the lateral prefrontal cortex. Generally, the amplitude of the hemodynamic response was reduced in patients in tight correlation with behavioral slowing during the Stroop task and with neuropsychological deficits, namely attentional and executive dysfunction. Interestingly, patients showed an early deoxygenation of blood right after stimulation onset, and a delay of the hemodynamic response. Whereas the amplitude of the hemodynamic response is reduced in the frontal lobes also with normal aging, data suggest that impairments of neurovascular coupling are specific for cerebral microangiopathy. In summary, our findings indicate frontal dysfunction and impairments of neurovascular coupling in cerebral microangiopathy.

Differential diagnosis of mesiotemporal lesions: case report of neurosyphilis

Sir, The September issue of Neuroradiology contained an interesting article by Vieira Santos et al. entitled “Differential diagnosis of mesiotemporal lesions: case report of neurosyphilis” [1]. Coincidentally, a paper by us on the same subject (the differential diagnosis of neuroradiologically apparent medial temporal lobe abnormalities [2]) was published in the September issue of the Journal of Neurology. As an author of the latter paper, I would like to make some remarks on the case report by Vieira Santos et al. [1]. The authors state that medial temporal lobe involvement in neurosyphilis had previously been described in only four patients. However, this statement is incorrect. First, the cited article by Kanamalla et al. does not include such a finding in the context of neurosyphilis. Second, as we document [2], although medial temporal lobe involvement in neurosyphilis can still be regarded as rare, it is not as rare as the authors suggest. In addition to the case report of Vieira Santos et al., as well as a report that was recently published in Neurology [3], at least 16 patients with this neuroimaging pattern can be found in the literature. With respect to its pathogenesis, we have already pointed out that the assumption of a meningovascular origin is questionable [2]. We would like to pose the questions: how do the authors interpret the discordant results of the serologic and CSF tests in syphilis and, as a result, which stage of syphilis do they see in their patient? Finally, the differential diagnosis of the clinical signs and symptoms of the patient include Lyme neuroborreliosis. Borrelia burgdorferi is well known as a confounder of serologic tests in syphilis [4]. As penicillin G may be a satisfactory treatment alternative in neuroborreliosis [5], the response to this kind of treatment cannot be regarded as a sufficient criterion of differentiation. We therefore ask whether the authors ruled out Lyme neuroborreliosis in this patient.

Neurosyphilis and paraneoplastic limbic encephalitis: important differential diagnoses

Sirs: A 34-year-old previously healthy heterosexual man with a history of alcohol and tobacco abuse was admitted to hospital after a first epileptic seizure. Neurological examination was unremarkable. Lumbar puncture was performed the same day with the following results: 4 cells/mm3, protein 953 mg/l. Non-contrast CT was normal. EEG showed generalized slowing and epileptiform discharges. At first, symptomatic epilepsy in the context of alcoholism was suspected. During the following days, repeated complex partial seizures developed. The patient was disoriented, anterograde and retrograde memory were severely impaired. On the 4th day, MRI showed a contrast-enhancing (T1-) hyperintense signal alteration in the left medial temporal lobe on FLAIR and T2-weighted images (Fig. 1a). Repeat CSF-analysis showed 22 cells/mm3, protein 952 mg/l, and positive oligoclonal bands. Serum/CSF tests for HSV 1/2, VZV, HIV 1/2 were negative. HHV-6-Ab titer in serum was 1:20 (IgG). VDRL in serum was positive, titer 1:8, in CSF 1:4. Quantitative TPPA-test in serum was 1:81920, in CSF 1:524288. Treponema pallidum IgG-Western Blot was positive in serum and CSF. Neurosyphilis (NSP) was diagnosed and IV penicillin treatment at a dose of 3 10 million units/d for 20 days was initiated. (Note: US Centers for Disease Control and Prevention recommended treatment for NSP [18]: penicillin G 18–24 million units/d administered as 3–4 million units IV every 4 hours or continuous infusion for 14 days). Because of the MRI findings suggestive of limbic encephalitis [7, 12], paraneoplastic limbic encephalitis (PLE) was considered as a differential diagnosis. Anti-neuronal antibodies (anti-Amphiphysin, -Hu, -Ri, -CV2, -Ma2) were negative. Whole body F-18FDG-PET showed a focal hypometabolism in the left medial temporal lobe and a circumscribed area of increased tracer uptake in the left upper lung (Fig. 1b). Thoracic CT correspondingly showed a hyperdense lesion of 1.6 cm in the left superior pulmonary lobe, suspicious of carcinoma. Wedge resection of the left superior pulmonary lobe was performed. Histopathological analysis showed a demarcated severe chronic inflammation with fibrosis (non-caseous degeneration). Treponema pallidum PCR was negative. There were no signs of malignancy. Under continuous anticonvulsant therapy no more seizures occurred. The patient’s state subsequently improved. However, after 8 months of follow up the patient still suffered from generalized cognitive slowing, impaired anterograde memoryand executive functions. Repeat MRI showed atrophy of left medial temporal lobe structures. Although NSP has become rare in industrialized countries [9], it has to be considered in a variety of neuropsychiatric disorders. PLE is another infrequent CNS disorder, which manifests itself in the presence of an – initially frequently occult – malignancy. Patients with PLE can harbor anti-neuronal antibodies, most often anti-Hu or antiMa2, which, however, are not obligatory [11]. Because of their unspecific or atypical clinical course, the spectrum of differential diagnoses of both diseases is wide. Particularly NSP has always been considered “the great imitator”. Nevertheless, to our knowledge these entities have never been reported as direct differential diagnoses. Clinical hallmarks of PLE are memory dysfunction, epilepsy, and psychiatric abnormalities [17]. The LETTER TO THE EDITORS

Intracerebral haemorrhage as a manifestation of Lyme Neuroborreliosis

Lyme Neuroborreliosis (LNB) has repeatedly been reported to cause cerebral vasculitis. However, there is no reliable information about the incidence of cerebral vessel affection. The majority of reports deal with ischaemic consequences, and there are a few reports of subarachnoid haemorrhage (SAH). We report a case of otherwise unexplained intracerebral haemorrhage (ICH) where clinical and laboratory tests have shown LNB. Late stage LNB might not only cause ischaemic, but haemorrhagic stroke as well.

Executive and behavioral deficits share common neural substrates in frontotemporal lobar degeneration — A pilot FDG-PET study

Behavioral and executive dysfunctions are typical symptoms of frontotemporal lobar degeneration, associated with its subtypes frontotemporal and semantic dementia. Although both functions depend on the frontal lobes, no study has yet compared their neural correlates in frontotemporal lobar degeneration. Accordingly, we correlated clinical scores of behavioral and executive deficits with glucose utilization as measured by [(18)F]fluorodeoxyglucose positron emission tomography in 17 patients with frontotemporal lobar degeneration and 9 age- and sex-matched control subjects. Impairment in executive functions was measured by the Behavioral Assessment of the Dysexecutive Syndrome, a modified Stroop paradigm and/or the Tower of Toronto Test. Behavioral deficits were examined with the Neuropsychiatric Inventory. Executive dysfunction was correlated with diminished glucose utilization in frontomedial and frontolateral cortices. Brain regions included the anterior cingulate and midcingulate gyri, anterior medial frontal cortex, and left frontolateral cortex. Behavioral deficits were associated with mainly frontomedial networks, particularly the anterior medial frontal cortex, gyrus rectus, and area subcallosa. Our pilot study reveals partially overlapping neural correlates of executive and behavioral dysfunction in frontotemporal lobar degeneration. The results suggest that some behavioral deficits, namely disinhibition and appetite and eating abnormalities, are particularly related to executive dysfunction. This hypothesis might be further explored in studies involving larger patient groups.

Clinical insights into paraneoplastic cerebellar degeneration

Neuroimaging is usually unremarkable in paraneoplastic cerebellar degeneration (PCD), at least in the early stages of the disease. A patient with proven PCD is reported in whom it could be shown that cerebellar atrophy evolved very rapidly and was present in early imaging studies. Even with the use of the whole spectrum of modern diagnostic tools, the underlying malignancy can be difficult to diagnose. In addition to mammography, MRI is recommended in these cases and repeat FDG-PET may be necessary.

Clinical findings in the chronic phase of traumatic brain injury: data from 12 years' experience in the Cognitive Neurology Outpatient Clinic at the University of Leipzig.

BACKGROUND There are many unresolved issues in the diagnosis and treatment of persons with traumatic brain injury (TBI) in its post-acute and chronic phases. This article deals with two problems of clinical importance: (i) the interrelationships between structural brain damage, brain function, and clinical outcome, and (ii) post-traumatic epilepsy. METHODS Exploratory, retrospective analysis of clinical, neuroradiological (MRI), and neuropsychological data of all patients with TBI who were treated in a cognitive neurology outpatient clinic of a German university hospital over a period of 12 years (n=320). RESULTS 156 patients (48.8%) had brain contusions, 83 of them (25.9%) as the sole neuroradiological abnormality. Traumatic micro-hemorrhages were seen in 148 patients (46.2%) and were the sole neuroradiological abnormality in 79 of them (24.7%). 49 patients (15.3%) had no structural brain lesion. There was no obvious correlation between the neuroradiological findings and the clinical outcome, as measured either by a general outcome parameter such as the extended Glasgow Outcome Scale (GOSE) or by neuropsychological testing. 47 patients (14.7%) had post-traumatic epilepsy; its occurrence was positively correlated with the presence of brain contusions, but not with an isolated diagnosis of diffuse axonal injury (DAI). CONCLUSION A comparison of the findings of neuroradiological studies and neuropsychological tests among patients in the chronic phase of traumatic brain injury does not reveal any simple relationship between structural and functional brain abnormalities. Diffuse axonal injury is often present in combination with other findings, and it may well be the only structural abnormality in many cases; therefore, all symptomatic patients should undergo MRI of the brain. Patients with isolated DAI seem to be less prone to post-traumatic epilepsy than those with brain contusions.

DEVELOPMENT OF MESIAL TEMPORAL LOBE EPILEPSY IN CHOREA-ACANTHOCYTOSIS

Chorea-acanthocytosis (ChAc) is a hereditary movement disorder that is caused by recessive mutations in the VPS13A gene on chromosome 9q21, encoding for chorein.1 Epilepsy is currently not considered a core clinical feature of ChAc, although approximately 40% of patients are affected by seizures. We report on 3 patients with mesial temporal lobe epilepsy as the first, predominant clinical indication, and in 2 of the patients so far the sole clinical symptom of the disease. For the first time in this context, a pathologic process in the medial temporal lobes, leading to hippocampal atrophy, is unequivocally documented. ### Case histories. Patient 1 was a 14-year-old boy when, after repeat epigastric sensations, a first seemingly generalized tonic-clonic seizure led to hospital admission. Several weeks prior, he had started to complain about repetitive deja vu. Repeat EEG studies most frequently showed normal 10/second alpha-, but also paroxysmal generalized theta-, right hemispheric delta-, and right temporo-occipital spike- and sharp-wave activity. Until the present, 4 years after the initial onset, 2 more tonic-clonic seizures have occurred, and, with variable frequencies, the patient continues to report rising epigastric sensations, deja vu, and amnesic auras. Medical treatment currently consists of the administration of topiramate (300 mg/day). Patient 2, the older brother of patient 1, had a first complex partial seizure at 23 years of age. His history was unremarkable; no febrile seizures had been reported. Lately, however, he has also reported repeat episodes of deja vu. EEG findings ranged from normal 9/second alpha- to intermittent and continuous spike- and sharp-wave activity over both frontotemporal regions. Apart from rare epigastric auras, the patient is presently (i.e., 8 months after his first epileptic seizure) seizure-free under levetiracetam (2,500 mg/day). Patient 3 is a 39-year-old man …