Chiari malformation type 1-related headache: the importance of a multidisciplinary study.

Chiari type 1 Malformation (CM 1) is a structural defect consisting of a displacement of the cerebellar tonsils through the foramen magnum causing obstruction of cerebrospinal fluid (CSF) outflow. CM 1 has a variety of presentation with headache being the most common symptom. The evaluation and treatment of headache related to CM 1 are often difficult, because the pain in the occipital-suboccipital region or headache that is of cough-type suggests symptomatic CM 1, but patients suffering from CM 1 can also report migraine or tension-type headache. In 2015 we started a collaborative project in which our group of neurologists, neurosurgeons and neuroradiologists contribute to create a Chiari Special Outpatient Service; this was set up to provide a multidisciplinary evaluation, treatment and follow-up of patient suffering from CM 1. 201 patients (58 males, 143 females) suffering from CM 1 were multidisciplinary evaluated. Headache characteristics, clinical features, and treatment of patients are discussed. Further progress in multidisciplinary care of headache and CM 1 should be performed to define guidelines.

Cranial ultrasound is a reliable first step imaging in children with suspected craniosynostosis.

PURPOSE: Skull radiography (SR) and Computed Tomography (CT) are still proposed as the first-line imaging choice for the diagnosis of craniosynostosis (CS) in children with abnormal head shape, but both techniques expose infants to ionizing radiation. Several studies shown that ultrasound may play an important role in the diagnosis of craniosynostosis. The aim of our study is to assess the diagnostic accuracy of cranial ultrasound scan (CUS) and confirm if it is a reliable first step imaging evaluation for the diagnosis of craniosynostosis in newborn. METHOD: A cohort of 196 infants (122/74 males/females), with a mean age of 4 months, clinically suspected to have abnormal closure of cranial sutures, were firstly examined by CUS and then referred to neuroradiologists to perform volumetric CT scan if the suspicion of stenosis was ecographically confirmed; otherwise, a routine follow-up and physical treatment was performed, to observe the evolution of the head shape. RESULTS: Of the 196 children studied by CUS, only two had inconclusive studies due to age limitation (>12 months). Thirty children were diagnosed with cranial synostosis at CUS and verified by CT; all the CUS results were confirmed, except two cases, that were revealed as false positives in the starting phase of the study. Twelve patients with very prominent head deformity and negative CUS underwent CT, which confirmed the CUS results in all of them; one case of closure of both temporal sutures, not studied by CUS, was documented by CT. All the 148 children with poor clinical suspicion and negative CUS underwent just a prolonged clinical follow-up. In all of them, a progressive normalization of head shape was observed, and the craniosynostosis was excluded on a clinical base. CONCLUSIONS: CUS is a highly specific and sensitive imaging technique. In referral centers, expert hands can use it as a reliable first-step screening for infants younger than 1 year, suspected to have a craniosynostosis, thus avoiding unnecessary exposure to ionizing radiation. The "golden age" to obtain the best CUS results is under 6 months of life. Because the method is operator-dependent and there is a learning curve, a case centralization is advisable.

Persistent orthostatic headache without intracranial hypotension: which treatment?

Orthostatic headache can be the leading symptom of intracranial hypotension, however, not all orthostatic headaches are due to cerebrospinal fluid leaks and these forms can be a clinical problem, especially for treatment. Aim of this study was to review patients with persistent orthostatic headache in whom a detailed head and spinal MRI follow-up did not reveal any sign of intracranial hypotension and to evaluate which treatment can be considered the first choice. Patients admitted to our headache center for evaluation of persistent orthostatic headache and followed after first admission with clinical and neuroradiological controls were systematically reviewed. 11 patients (7 M, 4 F) followed in a period lasted from 10 months up to 2 years were studied. Six patients (54, 5 %) reported a MRI performed previously elsewhere with a suspect diagnosis of intracranial hypotension which was not confirmed at MRI at our hospital such as during the radiological follow-up. Three patients (27.2 %) had developed orthostatic headache short after a neck or head trauma with no evidence of neuroradiological pathological signs and two patients (18 %) had a previous history of psychiatric disorder. We administrated antidepressants in five patients, atypical neuroleptic in three patients, association of antidepressant and antipsychotic in one patient and muscle relaxants in two cases. All patients showed a certain improvement of headache in the weeks after introduction of the pharmacological treatment; six (54, 5 %) had pain relief during the follow-up and five (45, 5 %) were pain free at the last clinical control. We found out that patients with the best outcome were the ones treated with antidepressants. Persistent orthostatic headache without any neuroradiological sign of intracranial hypotension is a challenging problem for clinicians. Although the International Classification of Headache Disorders (ICHD-3 beta version) criteria suggests the possibility of epidural blood patch in orthostatic headache without causes, we believe that a pharmacological treatment tailored on each patient should be always considered and antidepressants can be the first choice.

Resting state fMRI in cluster headache: which role?

The pathophysiology of cluster headache (CH) is not well-known. For several years, the most widely accepted theory was that CH was triggered by hypothalamus with secondary activation of the trigeminal-autonomic reflex. However, it was recently suggested that the posterior hypothalamus might be an actor of the pain modulating network more involved in terminating rather than triggering attacks. To investigate this hypothesis, resting state fMRI could provide valuable information on functional connectivity between brainstem and hypothalamus, as well as other brain structures that could be involved in CH pathophysiology. In this framework, here we review recent studies investigating functional connectivity by means of resting state fMRI. Despite the important findings of these studies, we suggest that important steps in the comprehension of CH pathophysiology will be done when the scientific community will use the new methodological approaches recently suggested to study functional connectivity in the brainstem.

Intracranial idiopathic hypertension: 1-year follow-up study.

Standard guidelines for ongoing management, as well as definitive data about the long-term course of idiopathic intracranial hypertension (IIH) are not available. The aim of this study was to compare several clinical and instrumental variables as assessed at the time of diagnosis and then after 1 year in a sample of IIH patients. A total of 21 patients were studied. Our results confirmed that headache and TVO are the most frequent symptoms in IIH patients, and that overweight is a very common feature. A trend towards a favorable outcome in patients followed for 1 year and treated by usual medical therapy was found: intracranial pressure was lower at follow-up; improvement of headache and transient visual obscurations, as well as of papilledema, was reported in most patients. On the other hand, neuroradiological findings (such as empty sella, perioptic subarachnoid space distension, narrowing of the transverse sinuses) were substantially stable at follow. These findings may be relevant for future research as far as understanding the role of different clinical and instrumental findings as diagnostic items as well as predictors of outcome in IIH.

Treatment of spontaneous intracranial hypotension: evolution of the therapeutic and diagnostic modalities.

Magnetic resonance imaging in patients affected by orthostatic headache often allows the diagnosis of spontaneous intracranial hypotension (SIH). Nevertheless, in the last 5 years, the diagnostic and therapeutic strategy for spontaneous intracranial hypotension (SIH) has been significantly modified. Specifically, all invasive techniques aimed at localization and demonstration of "spontaneous" spinal fistulas (myelography, isotopic cisternography, and so on) have been progressively abandoned. Also myelo-MR, although not an invasive exam, is no longer considered necessary to establish the most appropriate treatment. This change is due to the development and demonstration of a pathogenetic theory which considers the cerebrospinal fistula not as the primary cause of intracranial hypotension, but as the consequence of an imbalance between epidural and cerebrospinal fluid (CSF) pressures. In a consecutive series of 80 patients, we performed a standardized epidural lumbar injection of a dense compound aimed to raise the epidural pressure irrespective of the presence and site of CSF leaks. The technique used, the long-term results of this treatment and the diagnostic pathways will be discussed.

The "eye-of-the-tiger" sign may be absent in the early stages of classic pantothenate kinase associated neurodegeneration.

Pantothenate kinase-associated neurodegeneration (PKAN) is a rare disorder associated with brain iron accumulation. The brain MRI abnormality consists of T2 hypointensity in the globus pallidus with a small hyperintensity in its medial part, called the "eye-of-the-tiger" sign. We report on 2 patients affected by PKAN, in whom MRI examination did not demonstrate the "eye-of-the-tiger" sign in the early stages; the typical abnormalities were detected only in the following examinations. Case 1 is a 4-year-old boy first studied at age 2 years for psychomotor delay. The brain MRI was normal. In the following 2 years, the motor impairment progressed. The second brain MRI at age 4 years demonstrated the "eye-of-the-tiger" sign. Molecular analysis of the PANK2 gene revealed a missense mutation F228S in exon 2 in homozygosis. Case 2 is a 6-year-old boy first studied at age 2 years because of psychomotor delay. His brain MRI did not demonstrate abnormalities in the globus pallidus. In the following years spastic-dystonic tetraparesis became evident. A brain MRI at age 4 years demonstrated the "eye-of-the-tiger" sign. Molecular analysis of the PANK2 gene revealed a missense mutation in exon 5 (N501I). Our 2 cases demonstrate that the observation of a normal globus pallidus in the early stage of the disease does not exclude the diagnosis of classic PKAN.

Hemophagocytic lymphohistiocytosis with neurological presentation: MRI findings and a nearly miss diagnosis.

Hemophagocytic lymphohistiocytosis (HLH) is a rare disease with rarer neurological presentation. When this occurs, diagnosis may be delayed. This report aims to call attention to clinical, laboratory, and radiological features that should prompt the correct diagnosis. A 13-year-old girl presented with progressive increase in intracranial pressure and ataxia. MRI showed a diffuse tumor-like swelling of the cerebellum with tonsillar herniation and patchy white matter post-contrast enhancement. Regression of swelling with steroids ruled out glioma and medulloblastoma, and brain lymphoma was considered. Diagnosis of HLH was reached 2 months after onset when uncontrolled fever and severe elevation of liver enzymes occurred. Two bone marrow biopsies were needed to demonstrate hemophagocytosis. Familial HLH was confirmed by perforin gene mutations. Bone marrow transplantation was performed. The early diagnosis of HLH may be life saving. Awareness of the disease is necessary to investigate its characteristic findings, thus avoiding a delay in diagnosis.

Treatment of alterations in CSF dynamics.

Alterations of the intracranial pressure (ICP) may be present in several conditions. The aim of this brief review is to focus on two relatively rare conditions characterized by alterations in cerebro-spinal fluid dynamics--Spontaneous Intracranial hypotension (SIH) and Idiopathic Intracranial hypertension (IIH)--in which headache is one of the key symptoms. The most relevant clinical features, the expected MRI findings, and the therapeutic options regarding both conditions are discussed.

Application of IHS criteria to headache attributed to spontaneous intracranial hypotension in a large population.

We applied the recent International Headache Society (IHS) criteria for headache related to spontaneous intracranial hypotension (SIH) to 90 consecutive patients with a final diagnosis of SIH confirmed by cerebral magnetic resonance imaging with contrast. Orthostatic headache (developing within 2 h of standing or sitting up) was present in 67 patients (75%) but appeared within 15 min after standing or sitting-as required by point A of the criteria-in only 53 (59%). Forty-four (49%) patients did not satisfy point A, including 22 (24%) with non-orthostatic headache and 14 (16%) with headache developing >or= 15 min after standing or sitting up; 80 (89%) did not satisfy point D. Only three (3%) patients had headache fully satisfying the IHS criteria. These findings indicate that the current IHS criteria do not capture most patients with SIH-associated headache. Excluding the requirement for response to epidural blood patch (criterion D) and considering headaches appearing within 2 h of sitting or standing up would capture more patients.

Clinical features and outcomes in spontaneous intracranial hypotension: a survey of 90 consecutive patients.

Spontaneous intracranial hypotension (SIH) is a rare disabling condition whose main clinical manifestation is orthostatic headache. We analysed clinical characteristics in relation to time to resolution in 90 consecutive patients diagnosed with SIH at our centre between 1993 and 2006. After excluding 7 patients lost to follow-up, the remaining 83 cases were divided into four groups: Group A (53 cases) with progressively worsening orthostatic headache; Group B (3 cases) with severe acute-onset orthostatic headache; Group C (9 cases) with fluctuating non-continuous headache, of mild severity, that, in 33% of cases, did not worsen on standing; Group D (18 cases), 5 with a previous history of headache, 14 with orthostatic headache, and 10 with altered neurological examination. Complete symptoms and neuroradiological resolution occurred during follow-up in Groups A, B and D, but was longer in Group D probably in relation to more severe clinical picture with altered neurological examination. However, after a mean of 52 months (range 24-108), none of the nine Group C patients had MRI indicating complete resolution. The main characteristic of Group C related to incomplete resolution was delayed diagnosis. These preliminary findings suggest that early diagnosis of SIH correlates with better outcome, further suggesting that patients with a new headache that may worsen on standing or sitting should undergo MRI with contrast to expedite a possible SIH diagnosis, even if the pain is relatively mild.

POEMS syndrome: relapse after successful autologous peripheral blood stem cell transplantation.

We report a patient with POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, Skin changes) treated with high dose chemotherapy and auto-Peripheral Blood Stem Cell Transplantation (auto-PBSCT) who had a very good response with complete clinical remission. Seven years later, she relapsed and a new sclerotic bone lesion was found. To our knowledge, this is the first POEMS syndrome relapse after successful auto-PBSCT.

Artificial lamina-assisted laminoplasty performed in seven cases.

OBJECT: The authors attempted to simplify the operative approach to severe multilevel cervical spondylotic myelopathy. Seven patients with progressive and severe myelopathy underwent modified double-door laminoplasty during a 5-month period. METHODS: The double-door laminoplasty procedure was modified by using two artificial titanium laminae obtained by simple surgical 0.5-mm Ti-mesh (rather than by bone graft or ceramic spacers). Preoperatively, gait disturbance was present in all patients with long-tract signs on neurological examination. In all cases the sagittal diameter of the cervical spinal canal was somewhat reduced (< 10 mm) by congenital stenosis, and further severe compression of the spinal cord resulted from osteophytic bars and calcified ligamenta flava at different levels. No abnormal alignment, pathological movements, or instability was present. Computerized tomography (CT) studies demonstrated severe multilevel cervical compression, and T2-weighted magnetic resonance (MR) imaging demonstrated pathological areas of hyperintensity within the spinal cord in all cases. In the initial follow-up study (range 8-12 months), the patients who underwent this procedure experienced marked improvement of gait disturbance without any significant incidence of morbidity or complications. Postoperative CT and MR imaging studies demonstrated complete spinal cord decompression and restoration of the patency of the subarachnoid spaces. CONCLUSIONS: The proposed procedure has the advantage of achieving both an immediate stabilization of the open laminae by means of a bridgelike mechanism and protection from the possible compression of the dural sac by paravertebral muscles.

Diffusion tensor imaging shows different topographic involvement of the thalamus in progressive supranuclear palsy and corticobasal degeneration.

BACKGROUND AND PURPOSE: In progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), postmortem studies show different topographic involvement of the thalamus, basal ganglia, and their cortical connections. Diffusion tensor imaging (DTI) is an MR imaging technique sensitive to gray and white matter microstructure integrity. This study was performed to determine whether DTI may demonstrate microstructural differences between PSP and CBD, particularly within the thalamus and its cortical connections. MATERIALS AND METHODS: Nine patients with probable PSP, 11 with probable CBD, and 7 controls formed the study group. Apparent diffusion coefficient average (ADC(ave)) and fractional anisotropy (FA) values were measured in regions of interest positioned in the ventrolateral (motor), medial, anterior, and posterior regions of the thalami, basal ganglia, fronto-orbital white matter, cingulum, supplementary motor area (SMA), and precentral and postcentral gyri in patients and controls. RESULTS: In PSP, ADC(ave) values were increased in several areas: the thalamus, particularly in its anterior and medial nuclei; cingulum; motor area; and SMA. FA values were particularly decreased in the fronto-orbital white matter, anterior cingulum, and motor area. In CBD, ADC(ave) was increased in the motor thalamus, in the precentral and postcentral gyri, ipsilateral to the affected frontoparietal cortex, and in the bilateral SMA. FA was mainly decreased in the precentral gyrus and SMA, followed by the postcentral gyrus and cingulum. CONCLUSIONS: In patients with PSP, thalamic involvement was diffuse and prevalent in its anterior part, whereas in CBD involvement was asymmetric and confined to the motor thalamus. DTI may be useful in the differential diagnosis of these 2 parkinsonian disorders.

Can MR imaging diagnose adult-onset Alexander disease?

BACKGROUND AND PURPOSE: In recent years, the discovery that mutations in the glial fibrillary acidic protein gene (GFAP) were responsible for Alexander disease (AD) brought recognition of adult cases. The purpose of this study was to demonstrate that MR imaging allows identification of cases of AD with adult onset (AOAD), which are remarkably different from infantile cases. MATERIALS AND METHODS: In this retrospective study, brain and spinal cord MR imaging studies of 11 patients with AOAD (7 men, 4 women; age range, 26-64 years; mean age, 43.6 years), all but 1 genetically confirmed, were reviewed. Diffusion and spectroscopic investigations were available in 6 patients each. RESULTS: Atrophy and changes in signal intensity in the medulla oblongata and upper cervical spinal cord were present in 11 of 11 cases and were the diagnostic features of AOAD. Minimal to moderate supratentorial periventricular abnormalities were seen in 8 patients but were absent in the 3 oldest patients. In these patients, postcontrast enhancement was also absent. Mean diffusivity was not altered except in abnormal white matter (WM). Increase in myo-inositol (mIns) was also restricted to abnormal periventricular WM. CONCLUSIONS: Awareness of the MR pattern described allows an effective selection of the patients who need genetic investigations for the GFAP gene. This MR pattern even led to identification of asymptomatic cases and should be regarded as highly characteristic of AOAD.

Headache and spontaneous low cerebrospinal fluid pressure syndrome.

We examined 59 consecutive patients presenting between 1993 and 2006 at our centre diagnosed with headache associated with spontaneous intracranial hypotension syndrome (SIH). Thirty-six (61%) patients were women; the mean age was 47 years (range 20-68). Cerebral MRI with contrast confirmed SIH in all patients. Headache characteristics were obtained by direct semistructured interview; in a minority of cases information was completed retrospectively through a phone call. All SIH patients suffered from headache. Early recognition of SIH may avoid dangerous worsening due to delayed diagnosis. Orthostatic headache, the main symptom, suggests the diagnosis.