Gianfranco Cafforio

Functional magnetic resonance imaging in episodic cluster headache

We have investigated the cerebral activation centre in four patients with episodic cluster headache (CH) with functional magnetic resonance imaging (f-MRI). The patients underwent MRI scans for anatomical and functional data acquisition in the asymptomatic state, during a headache attack and after subcutaneous administration of sumatriptan. Anatomical images were acquired by means of 3D-MPRAGE sequences and f-MRI images were obtained by means of echo-planar imaging. Data was analysed using the BrainVoyager QX version 1.7.81 software package. In all patients, the data showed significant hypothalamic activation of the hypothalamus ipsilateral to the pain side, attributable to a headache attack. Overall, we have demonstrated the anatomical location of central nervous system activation by means the first f-MRI study in CH patients. f-MRI offers a good balance of spatial and temporal resolution, and this method of study appears appropriate for investigating the pathogenetic aspects of primary headaches. Positron emission tomography and f-MRI may be regarded as little or no importance in a clinical context, they do, however, offer great potential for the exploration of headache physiopathology and the effects of pharmacological treatment.

Ramsay-Hunt syndrome complicated by unilateral multiple cranial nerve palsies

Reactivation of the varicella-zoster virus (VZV) along the distribution of the sensory nerves innervating the ear, which usually includes the geniculate ganglion, is responsible for herpes zoster (HZ) oticus. When associated with facial paralysis, the infection is called Ramsay Hunt syndrome (RHS) [1]. Typically, RHS involves facial nerve unilaterally. Rarely other cranial nerves may be affected [2, 3]. Here we report an 82-year-old man who developed a hoarse voice, decreased hearing, difficulties in swallowing, nasal reflux and left facial droopiness five days after the onset of ear pain and fever. Crusted scars and an erythematous base on the external left ear were visible on examination. Neurological examination revealed hypoaesthesia of the 2nd branch of the left trigeminal nerve, together with the involvement of left VIIth (facial weakness), VIIIth (decreased hearing), IX and Xth (palatal and laryngeal paresis with dysphonia and dysphagia), XIth (weakness of the sternocleidomastoid muscle) and XIIth (leftward tongue protrusion) nerves. The clinical picture developed gradually over a few days. The first symptoms were dysphagia and facial weakness. Laryngoscopy revealed multiple ruptured vesicles and oedema of left hemi-pharynx and of the tongue. Cerebrospinal fluid (CSF) analysis showed increased protein levels, with normal cell count. Polymerase chain reaction for VZV was positive. CSF cytology was normal. MRI of the brain showed enhancement of left cranial nerves V, VII and VIII, and of the anterior condyloid canal (Fig. 1), as well as hyperintensity of the left hemipharynx (STIR T2-weighted image). Considered together the data suggested RHS with multiple cranial nerve involvement and intravenous treatment with acyclovir (10 mg/kg every 8 h daily for two weeks) and prednisolone (500 mg/day for 3 days) was therefore started. After 6 weeks, improvement of the facial weakness and dysphagia was observed, as well as recovery of sensitivity in the trigeminal nerve zone. However, the dysphonia and the sternocleidomastoid weakness remained unchanged. This is a quite atypical case in which the HZ oticus infection was complicated by a multiple unilateral palsy of the lower cranial nerves. From a clinical point of view the patient had involvement of the V, VII/VIII, IX, X, XI and XII left cranial nerves consistent with multicranial neuritis. An interesting aspect of our case report is the documentation of the inflammatory involvement of cranial nerves upon neuroimaging. In fact, the contrast-enhanced MRI demonstrates enhancement of some of these nerves: V, VII and VIII. Enhancement of the anterior condyloid canal could be related to inflammatory involvement of the XII nerve, Neurol Sci (2008) 29:497–498 DOI 10.1007/s10072-008-1022-2

Electrophysiological evidence by single fibre electromyography of neuromuscular transmission impairment in a case of Miller Fisher syndrome

Miller Fisher syndrome is an autoimmune neuropathy characterised by ataxia, areflexia and ophthalmoplegia, with minimal if any limb weakness, and in the majority of cases by high titres of IgG anti-GQ1b ganglioside antibodies. In vitro electrophysiological experiments have demonstrated that these antibodies induce a transmission blockade at neuromuscular junction either pre- or post-synaptically. We report the case of a 63-year-old man with MFS that shows blood serum negative for anti-GQ1b but presents an impairment of neuromuscular transmission detected by single fibre electromyography. To the best of our knowledge, this represents the first case in the literature using jitter technique and suggests that other antibodies may be involved in the function of motor end plates by bindings to the synaptic membranes.

Vertebral artery dissection onset mimics migraine with aura in a graphic designer.

Headache is the most common symptom in patients with cervical artery dissection. This symptom, however, rarely occurs in isolation, and more commonly is associated with other neurological symptoms and signs. Visual symptoms associated with vertebral artery dissection (VD) have also been observed, but do not typically mimic the migraine aura. Here, we report a young patient who presented VD, embolic ischemic lesions, and visual symptoms with the features of aura, followed by migraine headache. The suggestion of VD dissection should be kept in mind in those cases complaining of the first attack of headache that mimics migraine with aura. In these cases, an extensive neuroimaging study is advisable.

‘Indotest’ in Atypical Hemicrania Continua

Hemicrania continua (HC) is an indomethacin-responsive headache characterized by a chronic, strictly unilateral, side-locked without side-shifting, persistent headache. We report three cases of HC with atypical features in which an acute administration of indomethacin 50 mg IM (INDOTEST) was performed. In all three cases INDOTEST predicted chronic responsiveness to indomethacin. Thus, in cases of HC with atypical features, INDOTEST could help for a correct diagnosis and therapy.

Does sphenopalatine endoscopic ganglion block have an effect in paroxysmal hemicrania? A case report:

The authors report the case of a 69-year-old woman suffering from paroxysmal hemicrania (PH), intolerant to indomethacin and resistant to multiple therapies, in which sphenopalatine endoscopic ganglion block (SPG) dramatically modified the clinical outcome. SPG blockade could be considered a reasonable alternative in drug-resistant PH cases where indomethacin is contraindicated.

The first Italian family with evidence of pyramidal impairment as phenotypic manifestation of Silver syndrome BSCL2 gene mutation.

Silver syndrome (SPG17) is a rare form of hereditary spastic paraparesis. Its relationship to distal hereditary motor neuropathy (dHMN) type V is underlined by the recent discovery of causative mutation in BSCL2 gene coding for a protein termed seipin, an integral membrane protein of endoplasmic reticulum, with unknown function. Here we report the third Italian family with dHMN and SPG17 in which two affected members harbor the heterozygous N88S mutation in the BSCL2 gene. The proband developed a severe paraparetic spastic gait, while, in the other Italian families reported so far, no signs of upper motor neuron involvement were observed. This family confirms the clinical heterogeneity associated with this specific mutation. Moreover, this is the first report in which neuroimaging seems to confirm the pyramidal alterations in dHMN associated to SPG17.

Prevalence of right–to–left shunt in patients with cluster headache

Recent investigations documented that the prevalence of right–to–left shunt (RLS) in patients with migraine with aura (MA) is significantly higher than in healthy controls and similar to prevalence of RLS in young patients with cryptogenic stroke (CS). Nevertheless, little data are available in the literature about RLS prevalence in the other forms of primary headache. The aim of this study was to investigate the occurrence of RLS in patients with cluster headache (CH). We enrolled 30 consecutive patients with CH diagnosis according to the IHS criteria and 40 controls. RLS was assessed with bilateral transcranial Doppler contrast (TCDc) monitoring of middle cerebral arteries. Eleven patients (37%) resulted positive to TCDc monitoring for evaluation of RLS. These data show that the presence of RLS in this group is more prevalent than in the general population and similar to that found in MA and in CS.

Atypical Posterior Reversible Encephalopathy Syndrome in Puerperium

A 37-year-old woman with no significant past medical history presented on the 4th day of puerperium with sudden headache and severe bilateral visual disturbance (blurring and teichopsia) followed by isolated generalized tonic-clonic seizure. No other impairment was observed at neurological examination. Arterial blood pressure was consistently elevated (180/110 mm Hg). Blood and urine routine assays were normal, and no proteinuria was detected during both the pregnancy and puerperium. Cranial CT scan was unremarkable, whereas MRI FLAIR and FSET 2 sequences revealed scattered areas of increased signal in subcortical occipital and posterior parietal white matter, and more confluent areas of signal hyperintensity in the grey matter of the striatum, in the external and internal capsule bilaterally and in the upper brainstem ( fig. 1 a, b). Diffusion-weighted images (DWI) revealed signal isointensity or slight hyperintensity of the affected areas with an increase in the apparent diffusion coefficient (ADC) indicating vasogenic edema. MR venography was also performed to evaluate the deep venous system, and resulted normal. The patient was treated with labetalol 20 mg i.v. for 2 min followed by 40 mg i.v. at 10-min intervals until normalization of Dear Sir, Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiological entity characterized by headache, visual loss and epileptic seizures in a severe arterial hypertension setting due to hypertension-inducing diseases, such as renal diseases or eclampsia [1, 2] . Moreover, PRES can also be caused by hypertension-inducing treatments (i.e. erythropoietin, blood transfusion or immunosuppressants) [1] . Brain MRI typically documents vasogenic edema involving the occipitoparietal regions [3] as a result of loss of cerebral autoregulation related to hypertensive endothelial dysfunction and disruption of blood-brain barrier with increased permeability [4] . If PRES is diagnosed at the right time, both clinical signs and neuroradiological pattern are frequently reversible, whereas delayed diagnosis and treatment can lead to ischemic or hemorrhagic lesions with permanent neurological damage [4] . Edema can rarely involve the brainstem or the hemispheric deep structures. In this case, the resulting syndrome is called atypical PRES [5] . Misdiagnosis is a frequent event and involves vertebrobasilar ischemia, cerebral venous thrombosis and metabolic diseases. Here, we report two unusual cases of atypical PRES during puerperium with good outcome. Received: January 31, 2007 Accepted: May 22, 2007 Published online: January 29, 2008

Adie tonic pupil associated to endometriosis.

The tonic pupil is characterised by segmental palsies to light, cholinergic supersensitivity and light-near dissociation. The mechanisms underlying the tonic pupil are not fully understood, although axonal loss within the ciliary ganglion is believed to result in supersensitivity of the iris sphincteric muscle. The tonic pupil can also be associated with extra-ocular diseases such as diabetes, amyloidosis, vasculitides and neuropathies, either before or after the onset of such diseases [1]. A unilateral tonic pupil has also been described in the context of non-neurologic malignancies such as small cell lung cancers and seminoma and autoimmune pathways have been advocated as causative factors [2, 3]. We report on a young female patient affected with a tonic pupil, which resolved after treatment of her accidentally diagnosed asymptomatic ovarian endometriosis. A 31-year-old white female patient was referred to our institution for recent-onset anisocoria. No parasympatholytic drugs were taken. On clinical examination, visual acuity, perimetry, intraocular pressure, fundus and extraocular motility were normal. The left pupil was larger than the contralateral; transillumination of the left sphincteric muscle did not modify the pupil diameter. The tendon reflexes were normal as well as the overall neurological status. As previously reported [4], instillation of 0.0625% pilocarpine elicited a miotic effect in the affected pupil and no response in the contralateral one (Table 1). Cerebral and orbital MRI was normal. Blood exams, including immunologic and rheumatologic tests, were normal, apart from the serum level of Ca 125, which was increased to 375 IU/ml (n.v.<35 IU/ml). The patient’s serum was searched for anti-Hu, anti-Yo and anti-Ri antibodies, although with negative results. A subsequent abdominal CT scan revealed a multiloculated, solid left ovarian mass. The patient underwent surgical treatment of the neoplasm. Histology was consistent with endometriosis and the patient was administered progesterone immediately after surgery with improvement of her ocular symptoms. To our knowledge, this case is the first report of Adie tonic pupil associated with an endocrine dysfunction. Endometriosis consists of aberrant location of endometrial tissue outside the uterus. Recently, it has been speculated to be an autoimmune disease, owing to the presence of autoantibodies [5], nevertheless it may exhibit characteristics of malignancy, such as local invasion and metastasis and it may be associated with ovarian cancer [6]. Most neurologic paraneoplastic disorders are believed to be autoimmune diseases and antineuronal antibodies (i.e., anti-Hu, Anti-Yo and anti-Ri) are useful tools for the diagnosis of paraneoplastic conditions. Nevertheless antineural antibodies may be absent in paraneoplastic syndromes [7], as in the Neurol Sci (2006) 27:80–81 DOI 10.1007/s10072-006-0572-4