Claudia Giliberto

Transverse sinus stenoses persist after normalization of the CSF pressure in IIH

Background: Bilateral transverse sinus (TS) stenosis has been found in more than 90% of patients with idiopathic intracranial hypertension (IIH). Objective: To evaluate whether TS stenosis changed after normalization of CSF pressure in patients with IIH during medical treatment. Methods: Fourteen consecutive patients with IIH with bilateral TS stenosis on cerebral MR venography (MRV) during the medical treatment were studied. Patients were followed for over a 6-year period. During the follow-up, patients underwent repeated lumbar punctures (LPs) and cerebral MRV. MRV was always performed before each LP. Results: TS stenosis persisted in all the patients during the follow-up. In 9 of 14 (64%) patients with IIH, CSF pressure normalized during medical treatment. Conclusions: Transverse sinus (TS) stenoses, as revealed by MR venography, persist in patients with idiopathic intracranial hypertension after normalization of CSF pressure, suggesting the lack of a direct relationship between the caliber of TS and CSF pressure.

Bilateral transverse sinus stenosis predicts IIH without papilledema in patients with migraine

Background: The headache profile of patients with idiopathic intracranial hypertension without papilledema (IIHWOP) may be indistinguishable from that of migraine. Bilateral transverse sinus stenosis (BTSS) has been found in the majority of patients with IIHWOP. The frequency of BTSS associated with IIHWOP in patients with migraine is unknown. Objective: To detect the frequency of BTSS in adult patients with migraine and to investigate whether the presence of BTSS identifies patients with IIHWOP. Methods: In a prospective study from December 2000 to November 2005, 724 consecutive patients with recurrent headaches who fulfilled International Headache Society diagnostic criteria for migraine underwent cerebral MR venography (MRV). A portion of these patients underwent a lumbar puncture (LP) to measure CSF pressure. MRV and LP were also performed in 70 age-matched control subjects. Results: Six hundred seventy-five of the 724 patients with migraines had normal MRV. Seventy of these 675 patients underwent LP, and all of them had normal CSF pressure. Forty-nine (6.7%) of the 724 patients with migraine had BTSS. Twenty-eight of these 49 patients with BTSS underwent LP, and 19 (67.8%) had IIHWOP. The headache profiles of patients with BTSS and IIHWOP did not differ from those of patients with normal MRVs and CSF pressures within normal limits. CSF pressure was normal in both patients and controls with normal MRV. Conclusions: Of patients with migraine, 6.7% had bilateral transverse sinus stenosis; 67.8% of these patients had idiopathic intracranial hypertension without papilledema (IIHWOP). These results suggest that patients with migraine who present bilateral transverse sinus stenosis on cerebral MR venography should undergo lumbar puncture to exclude IIHWOP.

Bilateral transverse sinus stenosis and idiopathic intracranial hypertension without papilledema in chronic tension-type headache

Previous MR studies have established that bilateral transverse sinus stenosis (BTSS) predicts idiopathic intracranial hypertension without papilledema (IIHWOP) in migraine. However, it is uncertain whether BTSS identifies IIHWOP in patients with chronic tension-type headache (CTTH): using cerebral MR venography this study aimed to address this question.In a prospective study from February 2002 to December 2006, 198 consecutive patients with CTTH underwent MR venography. Of these patients, 58 underwent lumbar puncture to measure cerebrospinal fluid (CSF) pressure. MR venography and lumbar puncture were also performed in 45 agematched control subjects. BTSS was considered present when the signal flow was poor or lacking (flow gap) in the mid-lateral portion of both transverse sinuses. IIHWOP was diagnosed if the patient met the diagnostic criteria for idiopathic intracranial hypertension and did not have papilledema. Among the 198 patients with CTTH who underwent MR venography, 18 (9%) had BTSS. Thirteen of these 18 patients with BTSS underwent lumbar puncture, and nine (69.2%) had IIHWOP. CSF opening pressure was normal in all 45 patients as well as in all 45 controls with normal MR venography.These data suggest that BTSS on MR venography is associated with increased intracranial pressure in the absence of papilledema in patients with headache mimicking CTTH.

Posture-related cough headache and orthostatic drop in lumbar CSF pressure

Sirs: Primary cough headache (PCH) is an uncommon headache disorder marked by a sudden bilateral short-lasting pain precipitated by coughing in the absence of any intracranial disorder [1, 2]. In some patients with PCH, Symonds reported that vertical posture precipitated pain brought on by coughing [3]. We have seen two such patients (a 48-year-old man and a 31-yearold woman) with headaches lasting 1–10 min that were only triggered by coughing when the patients assumed a vertical posture, in whom we have also observed orthostatic drops in their CSF pressures. Neurological examination did not show any deficits. Contrast-enhanced head and spine MRI, and CSF examination findings were all normal. In these patients and in 25 controls (average age: 40.2 ± 7.7 years; 15 women and 10 men) none of whom had a history of headache or structural brain lesion, we recorded the lumbar cerebrospinal fluid (CSF) opening pressure at rest and during three to five coughs, in lateral decubitus, sitting and upright positions. In our patients lumbar CSF opening pressure recorded in lateral decubitus was within normal values (pressure of 153 and 164 mm H2O, respectively). In the sitting position lumbar CSF pressure was higher (330 and 310 mm H2O, respectively) than in lateral decubitus. In both positions a bout of coughing did not induce headache. Surprisingly, when the patients assumed the upright posture their lumbar CSF pressures dropped (160 and 165 mm H2O, respectively) compared with the values recorded in the sitting position, and a bout of coughing induced severe pain at the vertex. In the control group, postural changes (sitting and upright positions) always increased CSF lumbar pressure with more elevated value recorded in the upright posture (Figure). Coughing always increased CSF pressure regardless of positions, both in controls and in patients. The present findings demonstrate that our patients had posture-related cough headaches. Consistent with this observation, in the landmark paper entitled “Cough headache” Symonds [3] described four patients with PCH that was induced by the patients being in upright positions, whereas the patients could cough without pain when they were lying down. The Symonds’ study and the present cases suggest the possibility that in the minority of patients with cough headaches, the pain brought on by coughing can occur only in association with the vertical posture. In addition, our patients had orthostatic drops in their CSF pressures. This finding was never observed in controls in whom vertical posture always elevated their CSF pressures. As our patients had orthostatic headaches precipitated rather than aggravated by coughing, and they did not have imaging abnormalities of intracranial hypotension or low supine CSF pressures, spontaneous intracranial hypotension and abnormally low volume of CSF may be excluded [4–7]. Of note, some authors have recently demonstrated that patients with orthostatic headaches without LETTER TO THE EDITORS

Sporadic motor neuron disease in a familial novel SOD1 mutation: Incomplete penetrance or chance association?

Abstract Cu/Zn superoxide dismutase (SOD1) gene mutations have been reported in familial and sporadic amyotrophic lateral sclerosis (ALS). We report a novel G61R SOD1 mutation in a patient with a distinct phenotype including prominent lower motor neuron dysfunction, proximal weakness and atrophy with asymmetrical onset in the thigh and buttock and relentless clinical course. The G61R mutation segregated in three unaffected relatives including the 80-year-old mother and two of the probands siblings. Potential mechanisms include an autosomal dominant condition with reduced penetrance or a chance association.

Empty sella and bilateral transverse sinus stenosis predict raised intracranial pressure in the absence of papilloedema: a preliminary study.

Sirs: Empty sella (ES) is a radiological sign involving the sella turcica that is partially or completely filled with cerebrospinal fluid (CSF). A primary ES can occasionally be found as an anatomical variation, and may be due to congenital incomplete formation of the sellar diaphragm or volumetric changes in the pituitary gland [3, 4]. A secondary ES can be seen in several pathological conditions of the central nervous system, such as pituitary tumours or infective or traumatic diseases [3, 4]. An ES occurs in about 5–15 % of normal adults [2, 7] with a higher frequency in women and in older individuals [4, 7, 8]. Several studies have demonstrated that ES is associated with idiopathic intracranial hypertension (IIH) [2, 12], a disorder that can present with or without papilloedema [10, 13]. IIH is typically characterized by headache, transient visual obscuration, diplopia, tinnitus and papilloedema [13]. In the absence of papilloedema, however, the diagnosis may be difficult, and the presence of ES on Magnetic Resonance Imaging (MRI) is no sufficient cause to perform a lumbar puncture (LP) in order to measure CSF pressure. Recently, it has been found that the majority of patients with IIH with or without papilloedema had a stenosis of both cerebral transverse sinuses (TSs) on Magnetic Resonance Venography (MRV) [5, 9, 11], a finding rarely seen in normal controls [1, 9]. This finding suggests that venous hypertension may play a role in IIH, and that MRV can help to identify individuals suspected of having IIH. The purpose of our study was to investigate the significance of ES detected by MRI as an indicator of possible IIH in subjects with headache and normal MRI. To assess this issue we evaluated patients with ES on MRI for the signal flow of the transverse sinuses on MRV which is the technique of choice for detecting stenosis of cerebral venous sinuses [6]. MRVs were evaluated by the same neuroradiologist (F. F.), who was purposely unaware of each patient’s history. Informed consent was obtained from all participants in the study. Five-hundred and eighty-six consecutive individuals suffering from recurrent headache (474 women, 112 men) without neurological or ophthalmologic abnormalities and with normal MRI were enrolled between July 2002 and December 2004. Qualitative analyses of the sella turcica on midsagittal T1-weighted images were performed in all patients. The sella was considered completely or partially empty when it was filled with CSF more or less than 50 % respectively [4]. All the patients with ES underwent three-dimensional phase contrast (3-DPC) MRV. Bilateral TS stenosis was considered present when the signal flow was poor or absent (flow gap) in the mid-lateral portion of both TSs. A condition of partially or completely ES was found in 31 (4 men and 27 women) of 586 patients with headache (5.3 %). None of the subjects with ES had endocrine dysfunction. Eight (100 % women; mean age 40.0; mean BMI 36.6) of these 31 patients had bilateral TS stenosis on MRV (Figure), whereas the remaining 23 subjects (82.6 % women; mean age 52.8; mean BMI 30.0) had normal MRVs. Six of the 8 subjects with ES and bilateral TS stenosis underwent lumbar puncture, four of which revealed increased CSF pressure; 8 of the 23 subjects with ES and normal MRV underwent LP, all of which displayed normal CSF pressure (Table). The current results demonstrate that most patients (66.7 %) with both ES and bilateral TS stenosis had raised intracranial pressure while all the subjects with ES and normal TSs who underwent LP had normal CSF pressure. Although in the current study only a small number of patients was investigated by LP, our findings suggest that individuals suffering from headache without papilloedema who have ES on routine MRI should undergo MRV for evaluating signal flow in TSs and in presence of bilateral TS stenosis should undergo lumbar puncture to exclude IIH.

Subacute combined degeneration of the spinal cord presenting with pseudoathetosis of the upper limbs.

Vitamin B12 deficiency is usually associated with several neurological disorders, including myelopathy, neuropathy, neuropsychiatric symptoms, optic neuropathy, and sphincter dysfunctions. In adults, subacute combined degeneration (SACD) of the spinal cord is the common and more frequent neurological manifestation of vitamin B12 deficiency [1]. We report on a patient with pseudoathetosis of upper limbs, SACD, and vitamin B12 deficiency. A 75-year-old Caucasian man developed clumsiness and paresthesia (tingling) of the hands, in left more than in right one, on February 2010. One month later, he complained gait instability, progressive numbness in all extremities, weakness of the lower limbs, and urinary incontinence. His medical history included vitiligo and macrocytic anemia which were diagnosed 6 months before neurological manifestations. Neurological examination showed dystonic posture of the left arm, severe athetoid-like movements of fingers and hands at rest, mainly on the left side, worsened by eye closure and mental stress (counting backward); cranial nerve examination and muscle strength were within normal limits; loss of joint position was detectable and vibration sense was impaired below the elbow and at lower limbs, associated with decreased perception of touch, pain, and temperature in the limbs. Deep tendon reflexes were absent, and left plantar response was in extension. The gait was ataxic and Romberg’s sign present. MiniMental Status Examination scored 25/30 points. Blood analysis confirmed macrocytic anemia with red blood cells 2.94 x 10/mmc, hemoglobin 10.1 g/l, and mean cell volume 114 fl. Serum vitamin B12 level was markedly reduced (<30 pg/ml) with normal level of folate. Serum homocysteine level was normal. ANA, ENA, RA factor, antiphospholipid, lupus anticoagulant, gastric parietal cell, and intrinsic factor antibodies were absent. Thyroid function was normal. Biopsy obtained during gastroscopy disclosed ‘atrophic gastritis’. Neurophysiological examination found mild axonal sensory polyneuropathy. Visual evoked potentials and somatosensorial evoked potentials were impaired. MRI of brain was within normal limits. MRI of spinal cord revealed increased T2-weighted signal in the posterior columns from C1 through C5 level, without enhancement with gadolinium (Fig. 1). The patient was treated intramuscularly with cyanocobalamin 5000 lg daily for the first week and 1000 lg/week for further 6 months. After 6 months, his clinical conditions markedly improved. The patient was able to walk independently with resolution of paresthesias in the hands and feet and of sphincter disorders. Athetoid-like movements remarkably improved. Mean cell volume returned to normal parameters. MRI of spinal cord at 6 months’ follow-up did not show any changes. In the 19th century, Hammond defined ‘athetosis’ as involuntary movements leading to ‘an inability to retain the fingers and toes in position in which they might be placed and by their continual motion’ [2]. ‘Pseudoathetosis’ is defined as athetoid-like movements in association with severe proprioceptive sensory loss [3]. Spinal pseudoathetosis of upper limbs has been described in tabe dorsalis, syringomyelia, spinal trauma, migrated cervical disk, spinal tumors, multiple sclerosis, myelitis, motor neuron disease. Only in a few cases, spinal pseudoathetosis secondary to vitamin B12 deficiency has been reported [4,5]. It is well established that pseudoathetosis always occurs in association with a long-lasting severe proprioception deficit and hyperexcitability of motor neurons and interneurons, secondary to the loss of inhibition from sensory input, has been suggested to explain spinal pseudoathetosis. SACD is a pathological condition characterized by a direct damage of white matter and axons in the posterior columns of the spinal cord, with more severe changes in the cervical and upper thoracic cord, and relatively sparing of lateral columns. The anatomical localization of spinal lesion may explain how the proprioceptive sensory loss is more severe in the upper limbs. As a matter of facts, the proprioceptive sensory fibers of the upper limbs ascend in the cuneate fasciculus of the dorsal columns, whilst the sensory pathway of the lower limbs ascends in the gracile fasciculus only in the upper

Looks can be deceiving: three cases of neurological diseases mimicking Guillain–Barrè syndrome

Guillain–Barrè syndrome (GBS) is an acute, paralyzing, inflammatory peripheral nerve disease, featured by monophasic disease course, symmetrical limb weakness and areflexia. Several pathologies can mimic the clinical presentation of GBS, making hard the differential diagnosis for patients complaining of acute flaccid paralysis. In this paper we describe three cases of different neurological diseases presenting with acute motor symptoms mimicking GBS, reviewing the relevant literature on misdiagnosis of GBS.

A case of headache and idiopathic hypertrophic cranial pachymeningitis drastically improved after CSF tapping

A 70-year-old woman presented with a 8-month history of severe chronic headache with pain attacks lasting 1-2 hours, associated with bilateral tinnitus. Headaches were characterized by gravative pain, across the forehead and over the vertex, and partially improved during a 6-month period treatment with dexamethasone. She had a history of chronic myeloid leukemia. Neurological examination was normal. Brain magnetic resonance imaging (MRI) depicted diffuse leptomeninges thickening with gadolinium enhancement (Figure) and T2-hyperintense lesion on the frontal regions (Figure). Angio-MRI showed superior sagittal sinus subocclusion (Figure). Routine blood tests, urine, and cerebrospinal fluid (CSF) analysis were all normal. Body and brainpositron emission tomography (PET) excluded a secondary localization of limphoproliferative disease. A single-spot opening measurement and 1-hour monitoring of the CSF pressure (CSFP) were both elevated, respectively, 206 and 247 mmH2O (normal value: 65-200). A lumbar tap with removal of 30 mL of CSF was performed and CSFP was measured at the site of puncture afterward, showing a normal value. Headache gradually resolved over the following days. Repeated MRI at 1 week showed reduced thickness and enhancement of the affected dura mater and disappearance of the right frontal lesion (Figure). Over a 6-month interval, the patient was still pain free and a new MRI evaluation showed resolution of parenchymal lesion, further reduction in the pachymeningeal thickening and enhancement (Figure). Hypertrophic cranial pachymeningitis (HCP) is a rare fibrosing inflammatory process that involves the dura mater. A number of pathological entities may produce HCP including granulomatous diseases, tumors, en plaque meningioma, dural carcinomatosis, and infectious agents. Often the etiology remains unclear and HCP is labeled as “idiopathic” (IHCP). The main clinical features is chronic From the Dipartimento di Scienze Mediche, Chirurgiche e Tecnologie Avanzate G.F. Ingrassia, University of Catania, Catania, Italy (E. Reggio, C. Giliberto, and M. Zappia); Department of Diagnostic Imaging, Radiology Unit, Universitary Hospital Policlinico Vittorio Emanuele, Catania, Italy (G. Sortino)

Seated Man Walking: A Provocation Maneuver for Parkinsonian Tremor

Tremor is a classical clinical feature of Parkinson’s disease (PD), typically occurring as tremor at rest. Severity of tremor is related to the activities performed by patients; thus, mental stress, walking, or repetitive movements with another limb increase tremor amplitude, and provocation maneuvers are applied by clinicians in order to examine parkinsonian tremor. Among these, walking is a frequent activation method to observe and enhance PD tremor. We report on a new clinical provocation maneuver, that is, simulation of walking in the sitting position, allowing the appearance of tremor undetectable in these conditions. The patient was a 67-yearold farmer with no family history of neurodegenerative disorders. In 2013, he experienced progressive motor impairment. Neurological examination showed small steps gait with reduced right-arm swing, hypomimic face, hypophonic voice, neck and upper limbs rigidity, diffuse bradykinesia, and righthand resting tremor only present during walking. Other provocation maneuvers, such as backward counting, math calculation, and movement with another limb (either arms and legs), did not evoke tremor (see Video 1). He showed responsiveness to dopaminergic medication, and a diagnosis of PD was made. The patient also underwent electrophysiological study. Tremor activity was recorded by electrodes positioned over the extensor carpi radialis and flexor carpi ulnaris muscles. An accelerometer was placed on the right index finger. Because tremor was present only during gait, not triggered by other maneuvers, and the electromyography (EMG) registration was not feasible in these conditions, we decided to record tremor activity with the patient sitting on a chair with the arm fully supported against gravity, while simulating walking. We recorded an alternating pattern of resting tremor, with a frequency of 5 Hz. Afterward, we applied this test on 4 more PD patients (2 males, 2 females; mean age: 58.5 years; range, 54–66). Three of four patients showed tremor during simulated walking as well as during gait (see Video 1). Frequently, an exacerbation of the hand rest tremor is observed when asking parkinsonian patients to walk a short distance, as pointed out by Uchida et al. Several neuronal networks are involved in locomotion. The pedunculopontine nucleus (PPN) has an important role in initiation and maintenance of gait. It has been demonstrated that PPN is also engaged during limb movements and imagined gait. Motor planning is physiologically promoted and started by parietal, premotor, and supplementary motor cortical areas, the same regions also involved in the generation of tremor, as described by Timmermann et al. Besides, Bergman and Deuschl suggested that synchronous oscillating neuronal activity within the basal ganglia is responsible for parkinsonian symptoms and may be influenced and modulated by cerebellothalamic loop. The simulation of walking might activate the common areas involved both in gait control and in generation of tremor, despite the lack of balance essential for locomotion. In the present series, an EMG recording of tremor has been obtained with patients in the sitting position and simulating walking because they did not show tremor in the standing and sitting positions. An accurate EMG evaluation of tremor during walking is technically difficult. The new method proposed here allowed either to provoke the tremor or to adequately record it. The diagnostic value of this clinical maneuver could provide further suggestions to understand the mechanisms of provoked resting tremor in PD.