Daniel Kondziella

Thirty neurological eponyms associated with the nazi era.

In the 1920s, the neurosciences in Germany were world-class. Then came Hitler’s regime, and with it 2 distinct changes happened to the research milieus in Berlin and elsewhere. First, the persecution of Jews and others deprived Germany of many of its most outstanding scientists. Second, numerous German and Austrian physicians became active in National Socialist (NS)-euthanasia programs. In recent years, the medical community has become more aware of the ethical burden associated with eponyms derived from scientists of the Third Reich. Yet a list of these eponyms with emphasis on clinical neurology is still missing. This paper therefore reviews 30 neurological eponyms derived from 29 physicians who lived in the Nazi era. Among them are victims who were forced out of the country or murdered in concentration camps, protestors who risked their academic careers and often their lives, beneficiaries who published on brains from ‘euthanized’ children, and collaborators who were directly involved in the planning and execution of NS-euthanasia programs.

A ferritin tracer study of compensatory spinal CSF outflow pathways in kaolin-induced hydrocephalus

Spinal drainage of cerebrospinal fluid (CSF) into the lymphatic system is important in physiological and pathological conditions in both humans and rodents. However, in hydrocephalus and syringomyelia the exact CSF pathway from the central canal into the lymphatic tissue around the spinal nerves remains obscure. We therefore induced syringomyelia and hydrocephalus in 36 Lewis rats by injection of 0.1xa0ml kaolin into the cisterna magna. At 2, 4 and 6xa0weeks later cationized ferritin was stereotactically infused into the cisterna magna of controls and into the lateral ventricles of hydrocephalic animals followed by dissection of brain, spinal cord and spinal nerves. CSF pathway and tracer flow were studied by light and electron microscopy. We found that in rats with kaolin-induced CSF outflow obstruction, CSF passes from central canal syringes through ruptured ependyma and dorsal columns into the spinal subarachnoid space, from where it is absorbed along spinal nerves into extradural lymphatic vessels. Taken into account that spinal hydrostatic pressure in humans differs significantly from pressure in animals due to the upright gait, we conclude that spinal compensatory CSF outflow pathways might be of even greater importance in human hydrocephalus.

1H MR spectroscopy of gray and white matter in carbon monoxide poisoning.

Carbon monoxide (CO) intoxication leads to acute and chronic neurological deficits, but little is known about the specific noxious mechanisms. 1H magnetic resonance spectroscopy (MRS) may allow insight into the pathophysiology of CO poisoning by monitoring neurochemical disturbances, yet only limited information is available to date on the use of this protocol in determining the neurological effects of CO poisoning. To further examine the short-term and long-term effects of CO on the central nervous system, we have studied seven patients with CO poisoning assessed by gray and white matter MRS, magnetic resonance imaging (MRI) and neuropsychological testing. Five patients suffered from acute high-dose CO intoxication and were in coma for 1–6xa0days. In these patients, MRI revealed hyperintensities of the white matter and globus pallidus and also showed increased choline (Cho) and decreased N-acetyl aspartate (NAA) ratios to creatine (Cr), predominantly in the white matter. Lactate peaks were detected in two patients during the early phase of high-dose CO poisoning. Two patients with chronic low-dose CO exposure and without loss of consciousness had normal MRI and MRS scans. On follow-up. five of our seven patients had long-lasting intellectual impairment, including one individual with low-dose CO exposure. The MRS results showed persisting biochemical alterations despite the MRI scan showing normalization of morphological changes. In conclusion, the MRS was normal in patients suffering from chronic low-dose CO exposure; in contrast, patients with high-dose exposure showed abnormal gray and white matter levels of NAA/Cr, Cho/Cr and lactate, as detected by 1H MRS, suggesting disturbances of neuronal function, membrane metabolism and anaerobic energy metabolism, respectively. Early increases in Cho/Cr and decreases of NAA/Cr may be related to a poor long-term outcome, but confirmation by future studies is needed.

Spinal cerebrospinal fluid pathways and their significance for the compensation of kaolin-hydrocephalus.

AIMnTo study the mechanisms of CSF-outflow in hydrocephalus we used radiological and histological methods to examine pathways of CSF absorption. Two, four and six weeks after occlusion of the cisterna magna by kaolin solution, CSF-dynamics were determined. Direct magnification radiography was used to visualize the outflow of X-ray contrast. Ten rats in each group were sacrificed for histological analysis following ventricular perfusion with marker proteins. ICP was increased to 15 +/- 1 mmHg (mean +/- SD) compared to control animals (7 +/- 2 mmHg) in the four week group. Six weeks following kaolin injection no increase in ICP (6 +/- 1 mmHg) could be demonstrated. Outflow resistance was markedly raised in all animals (1074 +/- 315 mmHg min-1 ml-1) displaying highest values (2160 +/- 960) in the four week group as compared to control animals (504 +/- 71). Cisternography demonstrated blocked cranial absorption and CSF-outflow along lumbosacral nerve roots. Histological examination showed syrinx formation in the cervical and thoracic spinal cord. Marker proteins left the subarachnoid space along thoracic and lumbo-sacral spinal rootlets. The radiological and histological findings and the normalisation of ICP after six weeks at doubled CSF-outflow resistance indicated a recruitment of spinal perineural CSF outflow pathways for the compensation of the disturbed cranial CSF-absorption.

Hyperphosphorylation of tau protein in superficial CNS siderosis

In superficial CNS siderosis chronic subarachnoidal hemorrhage leads to hemosiderin deposits in the subpial layers of the brain and spinal cord. Many years usually pass between the initial event causing chronic bleedings and the development of cerebellar ataxia, sensory hearing loss and various sensorimotor deficits. The only therapeutic option is to identify and eliminate the bleeding source. Otherwise slow relentless decline to a bedridden state and dementia is usually unavoidable. However, it is not known how precisely leptomeningeal hemosiderin deposits induce progressive neurodegeneration. Here we present the first report of a patient with superficial CNS siderosis in whom cerebrospinal fluid biomarkers of brain damage were assessed. Levels of neurofilament light protein, glial fibrillary acidic protein, total tau protein and, most importantly, hyperphosphorylated tau protein were increased. The results indicate that in superficial CNS siderosis neurodegeneration may be secondary to iron toxicity and oxidative stress. Similar mechanisms have been suggested for other neurodegenerative disorders such as Alzheimers disease.

A diagnosis not to miss: pheochromocytoma during pregnancy.

Sirs: Pheochromocytoma during pregnancy is a life-threatening situation for both mother and fetus. Its diagnosis is too often missed [1, 2], mainly due to three reasons. Firstly, pheochromocytoma is extremely rare with an estimated prevalence in full-term pregnancies of 1 in 54,000 [3]; secondly, it has the ability to mimic a huge number of acute, insidious clinical syndromes and the tumor has been correctly termed the “Great Masquerader” [1]; thirdly, pheochromocytoma can be asymptomatic until delivery. Classic attacks include acute hypertension, headache, sweating and tachycardia. However, patients can be completely free of manifestations between attacks. Thus, diagnosis of pheochromocytoma during pregnancy remains a great challenge, but is essential to prevent disastrous complications for both mother and fetus [2, 4]. Although a few recent reports exist in the obstetric and anesthetic literature on this condition, curiously, to our knowledge there are no reports in recent neurological literature. A 30-year previously healthy woman in the 26th week of her first pregnancy was referred from her gynecologist because of new-onset headache. Symptoms had started six weeks earlier with pain in the neck, lightheadedness, nausea and vomiting after prolonged sunbathing. While all symptoms vanished with bed rest, a stabbing neck pain persisted, which during the next two weeks evolved into a daily occipital squeezing headache of mild intensity, intermingled with periodic pulsating neck pain. Subsequently, she developed episodic frontal throbbing headaches of moderate to severe intensity, accompanied by nausea, vomiting and hyperventilation. Episodes occurred up to five times daily and lasted from a few minutes to one hour. On two occasions the patient had noted a scintillating scotoma in the left visual field. She had no history of migraine. Since proteinuria and edema were absent, preeclampsia had been ruled out by her gynecologist prior to referral. Neurological examination, including fundoscopy, was unremarkable. The patient had no fever and blood pressure was 130/85 mmHg in both arms. Routine laboratory testing revealed mild leucocytosis and trombocytosis, slightly increased C-reactive protein and liver enzymes, but normal thyroid function and blood glucose. While the initial symptoms were consistent with aseptic meningitis secondary to heat stroke and prolonged sunbathing, the subsequent complaints were neither fully compatible with migraine nor with any other primary headache syndrome. MRI of the head including MR angiography and a lumbar puncture were normal and thus, cerebral venous thrombosis, vascular malformations, vasculitis, hemorrhagic and ischemic cerebrovascular accidents, infectious or neoplastic processes, and sinusitis were ruled out. However, on day three after admission the patient was observed during a severe headache with marked tachycardia, sweating, pallor, tremor and anxiety. Blood pressure was 220/110 mmHg, pulse rate 115 beats/min. A working diagnosis of pheochromocytoma was made. Repeated 24 hour urinary catecholamine testing revealed increased levels of norepinephrine (3,200–20,000 nmol; reference interval 62–560 nmol), epinephrine (240–620 nmol; 9–101 nmol), metanephrines (32–115 μmol; 5–7 μmol), aldosterone (260–280 nmol; 11–56 nmol) and vanillylmandelic acid (85–280 μmol; < 34 μmol). MRI of the abdomen showed a 6x6 cm solid right adrenal mass (Fig. 1). The patient’s family history was unremarkable for neuroendocrine tumors. Genetic testing of the patient for mutations of RET, VHL, SDHB and SDHD genes was negative. Using a multidisciplinary approach involving endocrinologists, anesthetists, surgeons and neonatologists, it was decided to treat the patient with phenoxybenzamine (α-adrenoceptor antagonist) and await fetal maturity. Headaches vanished completely. In the 31st week of pregnancy the patient underwent an uncomplicated caesarean section combined with removal of the adrenal mass. Microscopic evaluation confirmed the diagnosis of pheochromocytoma. Pheochromocytoma is a catecholamine-producing tumor arising from the adrenal medulla in 85 % of cases and in the remaining patients from chromaffin cells in or about sympathetic ganglia in the abdomen, pelvis, and rarely in the chest or neck [1]. Tumors with a comparable biochemical and clinical profile include some chemodectomas derived from the carotid body and neuroblastomas; the LETTER TO THE EDITORS

Cranial neuropathy in the blue rubber bleb nevus syndrome

A 75-year-old man presented in 2009 with sudden onset of a right-sided peripheral facial palsy and diplopia due to palsy of the right abducens nerve. During the last 10u2005years he had developed a large number of small bluish, compressible, rubbery and painless nodules involving primarily the face and trunk (figure 1A,B). Nodules were also found affecting the oral mucosa. Despite being treated for arterial hypertension, he was in a good general condition. MR Imaging of the brain in 2005, ordered during the evaluation of a minor stroke, had revealed multiple vascular anomalies in both the cerebrum and cerebellum. A skin biopsy from nodules of the chest had shown irregular dilated and congested vascular spaces, consistent with a venous malformation (figure 1C). A second MRI …

Brain CT perfusion in stroke in progression.

acute CT brain scan revealed subtle hypodensity of the left MCA territory with narrowing of the proximal MCA on CT angiography ( fig. 1 a). Due to symptom regression during the next 30 min and the unknown time of symptom onset, aspirin was given but not thrombolysis. The next morning she had minimal dysphasia and central facial paresis only (NIHSS score 2). However, her symptoms were fluctuating and on day 3 she again progressed to global aphasia. Brain CT with angiography was unchanged ( fig. 1 a). Brain CTP was performed, consisting of a 50-second series using cinemode scanning and nonionic contrast medium, which is believed to have no brain damaging effects during acute stroke [9] . A significant decrease of relative cerebral blood flow (rCBF) to approximately 30 ml/100 g brain tissue/min in the left MCA territory was seen ( fig. 1 b). Conventional angiography with angioplasty of the occluded M1 segment was performed. Due to immediate normalization of the blood flow we renounced stenting. After the procedure our patient again exhibited minimal dysphasia only. Brain CTP 2 days and angiography 8 days later showed complete restoration of rCBF to approximately 70 ml/100 g/min ( fig. 2 a and b). Magnetic resonance imaging on day 5 revealed minor infarcts in the left insular lobe and internal capsule. Despite extensive cardiovascular workup an embolic source was not found. Having made Dear Sir, Brain CT perfusion imaging (CTP) has been used to study cerebral blood flow (CBF) in acute ischemic [1] and hemorrhagic [2] stroke, vasospasm secondary to subarachnoidal hemorrhage [3] and in brain trauma [4] . CTP using new generation multislice scanners is a relatively recent technique with the potential of becoming a widely used tool of standard stroke assessment due to its better access in general medical emergency departments compared to magnetic resonance perfusion [5] . In patients with suspected acute stroke the site of vascular occlusion, infarct core, salvageable brain tissue and collateral circulation is best assessed by a combination of CTP and CT angiography [6, 7] . CTP may help decision-making for thrombolysis when there is no clear time of symptom debut [8] . Moreover, as shown below, CTP may assist decision-making for endovascular neuroradiologic treatment in patients with stroke in progression. To our knowledge, this is the first report of brain CTP in stroke in progression due to middle cerebral artery (MCA) occlusion.

The Sting in the Tail : Syncope and Palinopsia

Sirs: The symptom of persistent or recurrent images following the removal of the stimulating object is termed palinopsia (Greek; palin = again, opsis = vision) [1]. Like visual-spatial impairment palinopsia has been associated with lesions of the non-dominant occipital lobe [1, 2]. Hallucinations derived from the primary visual cortex (Brodmann area 17) occur as flashes or light spots. In contrast, sensations from the visual association cortex manifest as more detailed objects (area 18) or complex scenic hallucinations (area 19) [2]. The differential diagnoses include occipital lobe epilepsy, visual deprivation hallucinations, basilar migraine, psychotropic substances abuse and various psychiatric conditions. A previously healthy 64-year-old man had two episodes of syncope lasting five to ten seconds without any warning symptoms. The second syncope occurred while the patient was sitting down, talking to a visitor. Thirty minutes later he drove his car through his hometown. Although being familiar with the route, he had a feeling of derealisation and believed that this could not be his normal way. He got lost and had to ask several passersby for help. To his own surprise the journey lasted an hour instead of the usual five minutes. On admission he was conscious and fully orientated. Examination, including a full neurological assessment, was normal. Our patient did not have any psychotic symptoms, but claimed that his sight had become sharper while reading a newspaper in the waiting lounge. ECG, routine laboratory tests, brain CT and EEG during alertness and sleep were within normal limits. A lumbar puncture revealed only slightly increased cerebrospinal fluid albumin (524 mg/l). On the fifth day the patient maintained that he could see in his central vision a cartoon-like bright-colored wasp, which was projected on every object he focused on, e. g. the senior consultant’s nose during the ward round. Our patient had seen a picture of the wasp in the morning newspaper, but it did not disappear for two hours although he never looked at the newspaper again. He was aware that the wasp did not exist in reality. Later in the evening he had four new episodes of syncope and ECG monitoring revealed asystoles lasting up to 25 seconds (Fig. 1). A sick-sinus syndrome was diagnosed and he received a DDR pacemaker. Although free from further episodes of syncope, our patient experienced pseudohallucinations together or without derealisation up to several times per day. These symptoms were sometimes preceded by a rising epigastric sensation. A second interictal EEG with sleep deprivation remained normal. Brain MRI could not be performed because of his pacemaker. We made a clinical diagnosis of focal epilepsy with simple partial seizures and the patient received sodiumvalproate. After a couple of weeks all symptoms had resolved, but he was lost to follow-up. However, five months later, he developed headache, vomiting, lethargy and hemianopsia. CT revealed a glioblastoma multiforme involving the right temporal-occipital lobe (Fig. 2). Although the initial episode of derealisation together with visual-spatial impairment might resemble transitory global amnesia, these symptoms together with palinopsia and the feeling of a sharper sight were most likely due to partial seizures provoked by the developing glioblastoma multiforme in the occipital lobe. With the tumor invading the temporal lobe, features of temporal lobe epilepsy such as epigastric sensations occurred. On the first CT five months earlier, no signs of a tumor were visible, but contrast had not been given. While it is theoretically possible, that the patient suffered from both sick-sinus syndrome and a brain tumor, it is against the clinical rule that one should look for a single diagnosis combining all symptoms. Indeed, cardiac arrhythmias have been recognized as contributing significantly to sudden unexpected deaths in patients with focal epilepsy [3] and prevention by cardiac pacemaker has been advocated in a recent prospective longterm study [4, 5]. This case illustrates that both common symptoms such as cardiac syncope and uncommon ones such as palinopsia can be associated with a glioblastoma multiforme. A high level of suspicion and a thorough follow-up are necessary, since this connection might first become evident many months later.