Clinical predictors of therapeutic failure of occipital nerve stimulation in refractory chronic cluster headache.

BACKGROUND: Occipital nerve stimulation (ONS) is a treatment with evidence in refractory chronic cluster headache (CCH). However, the variable response rate and cost make it necessary to investigate predictors of response. METHODS: This is a cross-sectional study conducted through the review of medical records of CCH patients from six hospitals in Madrid. Epidemiological and clinical variables were compared between patients with ONS failure and the rest. ONS failure was defined as the need for device withdrawal or switch off because of lack of response or adverse events. RESULTS: From a series of 88 CCH, 26 (29.6%) underwent ONS surgery, of whom 13/26 (50.0%) failed because lack of response. ONS failure group had an earlier headache onset (mean ± SD) of 27.7 ± 6.9 vs. 36.7 ± 11.8 years, p = 0.026) and a higher smoking rate (100% vs. 42.9%, p = 0.006). Stational fluctuations (58.3% vs. 7.7%, p = 0.007) and nocturnal exacerbations (91.7% vs. 53.9%, p = 0.035) were more frequent in the ONS failure group as well. There was no difference between groups in diagnostic delay, years of evolution prior to surgery, mental illness, comorbidity with other headache disorders or chronic pain conditions or prior response to occipital nerves anesthetic blocks. CONCLUSIONS: Some clinical features such as an early debut, smoking and seasonal or circadian fluctuations could be related to failure of ONS in refractory CCH.

Real-world experience of OnabotulinumtoxinA treatment in female patients with chronic migraine: a qualitative study using in-depth interviews.

BACKGROUND: Chronic migraine (CM) causes great disability and affects an individual's quality of life. OnabotulinumtoxinA (OBT-A, Botox®) was the first prophylactic treatment specifically indicated for CM. The aim of this study was to describe the experiences of women with CM treated with OBT-A. MATERIALS AND METHODS: The study design is a qualitative descriptive study. A purposeful sampling of 30 women (mean age, 42.7; standard deviation, 10.6) who had received at least two administrations of OBT-A for CM (PREEMPT protocol) was performed. Data collection included in-depth interviews and researchers' field notes. A thematic analysis was carried out according to qualitative research guidelines. RESULTS: Five themes were identified: (a) A long way to go before Botox®, (b) First time hearing about the treatment and its expectations, (c) The administration of Botox®, (d) Treatment effects, and (e) Follow-up. Patients described a long history of treatment failures prior to the start of OBT-A treatment. Information about this migraine treatment came from the neurologist; following the information, patients had high expectations, including unrealistic expectations regarding the onset and duration of effect. They acknowledged fear of the injections and some discomfort due to the procedure. With treatment, participants reported better migraine control and an improvement in their quality of life. Follow-up had some barriers, such as delayed appointments for subsequent doses, but also strengths, such as effectiveness and few side effects. CONCLUSIONS: Qualitative research offers insight into how patients with CM experience treatment with OBT-A. Our results highlight some relevant aspects that should be considered when providing OBT-A treatment.

Women had unrealistic expectations regarding the onset and duration of OBT-A effect.With OBT-A treatment, women perceived better migraine control and improved quality of life.Follow-up had barriers, such as delayed appointments for subsequent doses.

Epicranial headaches part 2: Nummular headache and epicrania fugax.

BACKGROUND: Nummular headache and epicrania fugax are two primary headaches that fall under the heading of epicranial headaches. METHODS: This article reviews the epidemiological and clinical features of nummular headache and epicrania fugax, proposed pathogenic mechanisms and state-of-the-art management, according to the literature. RESULTS AND CONCLUSIONS: Nummular headache and epicrania fugax are generally viewed as rare headache disorders, but no population-based epidemiological data are available. Nummular headache is characterized by continuous or intermittent head pain, which remains circumscribed in a round or oval area of the scalp, typically one to six centimeters in diameter. Epicrania fugax manifests with brief paroxysms of pain that move along the surface of the head, following a linear or zigzag trajectory through different nerve territories. Nummular headache and epicrania fugax are mostly primary headaches, but some secondary cases have been reported. The pathogenesis of these headaches is not fully understood. Nummular headache could probably originate in epicranial tissues or adjacent intracranial structures, while the origin of epicrania fugax could be extracranial or intracranial. Diagnostic assessment requires careful examination of the symptomatic areas. Underlying disorders should be excluded by additional investigations, including neuroimaging and appropriate blood tests. No controlled clinical trials have been conducted in nummular headache or epicrania fugax. Analgesics and anti-inflammatory drugs, botulinum toxin and gabapentin are currently the most recommended treatment options for nummular headache. In epicrania fugax, the most used treatments are gabapentin, lamotrigine, and other antiseizure medications.

Nummular headache responsive to anti-calcitonin gene-related peptide monoclonal antibodies in a patient with migraine.

BACKGROUND: Nummular headache (NH) is defined by the presence of localized pain circumscribed to a round or elliptical area of the scalp, with a well-defined contour and a diameter of 1-6 cm. Although some evidence supports a peripheral mechanism, its etiopathogenesis remains unclear. CASE: We report the case of a 64-year-old man with high-frequency episodic migraine who has used topiramate, beta-blockers, flunarizine, and amitriptyline without effect. In the last 8 years he also had continuous pain in an oval area of the scalp, consistent with NH. Triptans were ineffective for this new pain, and preventive therapy with gabapentin and onabotulinumtoxinA in the painful area had no effect. NH remitted when the patient received monthly treatment with subcutaneous galcanezumab for his migraine. CONCLUSIONS: Monoclonal antibodies against calcitonin gene-related peptide (CGRP), in particular galcanezumab, might be an effective therapy in some patients with NH. CGRP may have a role in the etiopathogenesis of this headache, which warrants further investigation.

Sensory processing and adaptive behavior in Phelan-McDermid syndrome: a cross-sectional study.

Phelan-McDermid syndrome (PMS) is a genetic disorder caused by a mutation or deletion of the SHANK3 gene (chromosome 22q13.3), characterized by different sensory processing anomalies. The objective of this study is to expand and provide a detailed definition of the sensory profile of patients with PMS. The secondary objective was to examine the relationship between sensory patterns and adaptive behavior. A cross-sectional study was carried out among 51 Spanish patients with a confirmed genetic diagnosis of PMS. All the participants' parents completed the Short Sensory Profile-Spanish (SSP-S) and the Adaptive Behavior Assessment System II (ABAS-II). Correlational, multiple regression and hierarchical cluster analyses were performed. An atypical sensory profile was identified in almost 75% of PMS patients. Definite differences were found among scores; nonetheless, sub-threshold values were observed in tactile sensitivity, underresponsive/seeks sensation, auditory filtering, and low energy/weak sensory categories. Conceptual, social, and practical domains, as well as the General Adaptive Composite (GAC) of the ABAS-II showed extremely low scores (i.e., <70). Significant correlations were found (p<0.005) between SSP-S scores and the conceptual, social, practical, and GAC index of the ABAS-II, whereby higher SSP-S scores were associated with better skills and higher adaptive performance. The cluster analysis indicated that the group with the largest mutation size (7.23 Mb) showed the greatest sensory processing difficulties and very low adaptive skills. CONCLUSIONS: Patients with PMS show an atypical sensory profile, which correlates with limitations in general adaptive behaviors. WHAT IS KNOWN: • PMS sensory processing difficulties were associated with a pattern of underresponsive/seeks sensation, low energy/weak, and tactile hyporeactivity. • Sensory processing difficulties have been associated with limitations in the development of appropriate adaptive communication and interaction behaviors. WHAT IS NEW: • Sensory definite differences associated with tactile hyperreactivity, as well as significant effects of underresponsiveness/seeks sensation and auditory filtering categories on the adaptive abilities were found in SHANK3deletion patients. • Cluster analysis suggests that smaller mutation sizes were related to better sensory processing and higher adaptive skills, while patients with larger deletion sizes have greater adaptive difficulties and worse sensory processing skills.

Understanding the diagnoses and medical care experience of patients with new daily persistent headache: a qualitative study in Spain.

OBJECTIVE: To explore the experiences of patients suffering from new daily persistent headache (NDPH) regarding the diagnostic process, treatment and medical care. DESIGN: A qualitative phenomenological study was conducted. SETTING: A specialised headache unit at two university hospitals in Spain between February 2017 and December 2018. PARTICIPANTS: Patients diagnosed with NDPH according to the International Classification of Headache disorders (third beta edition). METHODS: Purposeful sampling was performed. Data were collected using unstructured and semistructured interviews, researchers' field notes and patients' drawings. An inductive thematic analysis was used to identify significant emerging themes from interviews, field notes and descriptions of patients' drawings. Also, Guillemin's proposal was used to analyse the contents of drawings. RESULTS: Nineteen patients with a mean age of 45.3 were recruited. Four main themes emerged: (1) Seeking a diagnosis, patients visit many doctors without receiving a clear answer and their diagnosis is delayed; (2) Self-medication-minimising pill intake, medication is ineffective, and therefore, some patients discontinue treatment, or are flexible with how they take medication; (3) Trying other non-pharmacological options, many patients turn to other therapies and complementary and/or alternative therapies as a second option, however these are ineffective and (4) Medical care, with two subthemes, referrals and lacking continuity of care, and building the doctor-patient relationship. Patients describe how the referral breaks the continuity of care, and how they identify the traits of a doctor who is approachable and which behaviours the doctor should avoid when caring for patients. CONCLUSIONS: An in-depth knowledge of the beliefs and expectations of patients with NDPH will allow the professional to establish a relationship of trust, which will improve the patients' knowledge of which therapies are the most appropriate, and to establish expectations based on the relationship with the doctor, and not only on patients' beliefs.

Epidaily, a scale for comprehensive functional assessment of patients with epilepsy.

OBJECTIVE: To develop and validate an epilepsy-specific scale for comprehensive functional assessment of patients with epilepsy, named Epidaily. METHODS: The multidisciplinary research group created through brainstorming a list of 47 items to explore the cognitive, social, basic and instrumental functionality of the patient. A group of epilepsy experts independent of the research group evaluated the suitability of all the items, which then were selected and reviewed by the research group to conform the Epidaily scale. On a sample of 102 patients, a reliability analysis was performed, as well as a validation one using as reference scale the score on the Activities of Daily Living Questionnaire (ADLQ), which evaluates basic and instrumental functionality. RESULTS: Epidaily consisted of 10 items distributed in four dimensions, with a possible score from 0 to 100 (perfect functionality). Inter-observer reliability was excellent, with an intraclass correlation coefficient of 0.98 (95% confidence interval 0.97-0.99). Criterion validity was demonstrated by the high positive correlation of the Epidaily score with the ADLQ score (Spearman's rho coefficient 0.85, p < 0.001). Significant relation was found between ADLQ and Epidaily in the linear regression analysis (p < 001), which reported that Epidaily explains 85.5% of the variability of ADLQ (R-squared 0.85). Discriminant validity was also proved, as Epidaily allowed to classify epilepsy severity based on Cramer et al epilepsy severity classification. The median time to obtain the Epidaily score was 5 min (interquartile range 4-6). SIGNIFICANCE: Epidaily is a brief and versatile scale, with excellent inter-observer reliability, which has been validated for comprehensive functional assessment of patients with epilepsy.

Therapy delay in status epilepticus extends its duration and worsens its prognosis.

BACKGROUND: Timing in status epilepticus (SE) attention is probably the most relevant modifiable prognostic factor and may influence SE duration and prognosis. We aimed to describe the precise relationship between management timing, duration, and prognosis of SE. METHODS: Observational longitudinal prospective study on a cohort of all patients diagnosed with SE admitted to our tertiary hospital from September 2017 to August 2019, with a 3-month follow-up. Univariate and multivariable analyses were performed to identify clinical and timing variables associated with SE duration and prognosis. RESULTS: Eighty-three SE affecting 76 patients were included. Median age was 73 years, 61.4% were women, median baseline modified Rankin Scale (mRS) was 2, and 55.4% had prior epilepsy. In the out-of-hospital group (n = 50), median time to emergencies was 1.3 h and to hospital admission 2.8 h. In the global series, median time to neurologist was 4.3 h, and median time to therapy initiation was 4.5 h. These four times positively correlated with SE duration (all Spearman's rho coefficient >0.5, all p < .001). SE median duration was 24 h and was extended 1.2 h for each hour of treatment delay. A longer SE duration was associated with increased mortality and morbidity, both at hospital discharge and at 3-month follow-up (both p < .05). After 3 months, mortality was 30.1%, while recovery to baseline mRS occurred in 39.5%, with an overall median mRS of 4. CONCLUSIONS: There were pervasive delays in all phases of SE attention, which conditioned a longer SE duration, and this led to increased long-term morbimortality.

The clinical, histologic, and genotypic spectrum of SEPN1-related myopathy: A case series.

OBJECTIVE: To clarify the prevalence, long-term natural history, and severity determinants of SEPN1-related myopathy (SEPN1-RM), we analyzed a large international case series. METHODS: Retrospective clinical, histologic, and genetic analysis of 132 pediatric and adult patients (2-58 years) followed up for several decades. RESULTS: The clinical phenotype was marked by severe axial muscle weakness, spinal rigidity, and scoliosis (86.1%, from 8.9 ± 4 years), with relatively preserved limb strength and previously unreported ophthalmoparesis in severe cases. All patients developed respiratory failure (from 10.1±6 years), 81.7% requiring ventilation while ambulant. Histopathologically, 79 muscle biopsies showed large variability, partly determined by site of biopsy and age. Multi-minicores were the most common lesion (59.5%), often associated with mild dystrophic features and occasionally with eosinophilic inclusions. Identification of 65 SEPN1 mutations, including 32 novel ones and the first pathogenic copy number variation, unveiled exon 1 as the main mutational hotspot and revealed the first genotype-phenotype correlations, bi-allelic null mutations being significantly associated with disease severity (p = 0.017). SEPN1-RM was more severe and progressive than previously thought, leading to loss of ambulation in 10% of cases, systematic functional decline from the end of the third decade, and reduced lifespan even in mild cases. The main prognosis determinants were scoliosis/respiratory management, SEPN1 mutations, and body mass abnormalities, which correlated with disease severity. We propose a set of severity criteria, provide quantitative data for outcome identification, and establish a need for age stratification. CONCLUSION: Our results inform clinical practice, improving diagnosis and management, and represent a major breakthrough for clinical trial readiness in this not so rare disease.

Paroxysmal headache with extracephalic irradiation: Proposal for a new variant of epicrania fugax in a series of five patients.

BACKGROUND: Epicrania fugax consists of brief paroxysms of pain, which radiate in a line or in zigzag trajectory across the surface of the scalp or the face. METHODS: A prospective, descriptive study was performed in five patients presenting with an epicrania fugax-type pain with extracephalic irradiation. RESULTS: All patients were women, and the mean age at onset was 59.8 (standard deviation, 10.9). They had unilateral paroxysms of electrical pain starting at a particular point in the head (parietal, n = 3; vertex, n = 1; frontal, n = 1) and rapidly radiating downwards in a lineal trajectory to reach extracephalic regions (ipsilateral limbs, n = 2; shoulder, n = 2; low neck, n = 1) in 1-3 seconds. Pain intensity was moderate or severe. Three patients had nummular headache at the point where the paroxysms originated. One patient had spontaneous remission, and four patients achieved complete or almost complete response with therapy (onabotulinumtoxinA, n = 2; indomethacin, n = 1; amitriptyline, n = 1; lamotrigine, n = 1). CONCLUSION: The spectrum of epicrania fugax may include paroxysms with extracephalic irradiation. The propagation of pain beyond the head and the face supports the involvement of central mechanisms in the pathophysiology of this entity.

The Day My Life Changed: A Qualitative Study of the Experiences of Patients With New Daily Persistent Headache.

OBJECTIVES: This study aimed to explore the views and experiences of a group of Spanish patients suffering from new daily persistent headache (NDPH). METHODS: A qualitative descriptive study was conducted with patients diagnosed with NDPH. Purposeful sampling was performed among patients attending a specialized Headache Unit at 2 university hospitals between February 2017 and December 2018. In total, 18 patients (11 women, 7 men; mean age 45.3, standard deviation 10.6) with a median duration of illness of 70 months (interquartile range, 24-219) were recruited to this study. Data were collected through in-depth interviews, researchers' field notes and patients' drawings. Thematic analysis was used to identify emerging themes. RESULTS: Three main themes were identified: (1) the origin of the illness and seeking answers; (2) characteristics of the pain; and (3) the impact of pain on patients' lives. The patients precisely recalled the time of onset and the trigger of the pain. Pain was constantly present, although it varied in form. At the onset, pain was perceived as a sign of alarm while, over time, it became an invisible illness. The headache commonly had a major impact on everyday life and could cause lifestyle changes. In addition, pain could be emotionally disruptive and could also lead to family estrangement and a search for solitude. CONCLUSIONS: Our results provide insight into how NDPH is experienced, which may be helpful in managing NDPH patients. In our cohort, patients identified precipitating events but sought answers regarding the origin of their illness and their pain. Pain was a continuous sensation that had a major impact on patients' daily lives and emotions.

Patients' knowledge on epilepsy and SUDEP improves after a semi-structured health interview.

BACKGROUND: Patients' education is the most relevant contributor to patient self-management of epilepsy. We aimed to assess the acquisition of knowledge after a semi-structured interview. METHODS: We performed a quasi-experimental prospective study with a cohort of patients with epilepsy admitted for prolonged video electroencephalogram (VEEG). We measured patients' baseline knowledge with a 10-item true-false test (test A). Then, a qualified nurse carried out a semi-structured interview. We measured acquired knowledge with another 10-item true-false exam (test B), prior to VEEG discharge and after a 3- to 5-month follow-up, and we compared the difference between the scores in test A and test B. Finally, we conducted a satisfaction and suitability survey on the interview at follow-up. RESULTS: Thirty-two patients participated, half were women. Their median age was 39.5, and the median length of schooling was 14 years. The median time since epilepsy onset was 13 years, 75% had suffered tonic-clonic seizures. The median score on test A was 7, while the median score on test B was 8.5 (p < 0.001) both at VEEG discharge and after follow-up. After the interview, 84.4% of participants reported that they were very satisfied with the information received; 87.5% stated that they had not previously heard about SUDEP (sudden unexpected dead in epilepsy); and 93.8% considered it important to receive detailed information about SUDEP. CONCLUSIONS: Patient education through a semi-structured comprehensive interview improves knowledge of patients with epilepsy about their disease. The calm atmosphere and the qualified nursing working at VEEG units make them an appropriate setting for talking about epilepsy and its risks, including SUDEP.

Self-reported periodontitis and migraine: results from a multicenter, cross-sectional survey in Spain.

The aim of this study was to evaluate self-reported periodontitis (PD) prevalence in migraineurs as well as to investigate the association between both diseases. A cross-sectional survey was carried out including patients diagnosed with migraine attending 12 Spanish Headache Units. We determined diagnosis of PD administering a validated self-reported questionnaire. Socio-demographic, clinical and medical information, comorbidities, daily habits, migraine characteristics and medication were collected using a questionnaire. Of the 651 consecutive migraineurs included in the study, 393 suffered from chronic migraine (CM). Self-reported PD was detected in 327 patients with migraine (50.2%). Migraineurs with self-reported PD were significantly older and had a previous history of fibromyalgia, stress, anxiety, depression, and allodynia (all P < 0.001). Additionally, this group of patients consumed more topiramate (P = 0.008) and simple analgesics (P < 0.001) than patients with migraine and without self-reported PD. Also, they were less active physically and belonged to a low education level (both P < 0.001). Prevalence of self-reported PD was significantly higher in chronic migraineurs compared to those diagnosed with episodic migraine (EM) (53.9% vs. 44.6%, P = 0.019). Logistic regression analyses showed that self-reported PD was associated with CM (OR 1.456; 95% CI 1.062-1.997, P = 0.020). However, after adjusting for significant confounders, the association was attenuated (OR 1.100; 95% CI 0.784-1.543, P = 0.581). We concluded that self-reported PD was significantly more frequent in CM compared to EM. Self-reported PD was associated with the presence of CM, although some comorbidities shared by both diseases could have an effect on this association.

Paroxysmal pressing headache: A new short-lasting headache.

INTRODUCTION: In this report we describe a series of patients with a previously undescribed headache. METHODS: Over a 4-year period, we recruited 14 patients with a distinctive type of head pain of unknown cause that did not meet diagnostic criteria for other primary headaches. RESULTS: Nine women and five men with a mean age of 49.6 years (standard deviation, 17.8) presented with spontaneous headache attacks lasting 2-15 minutes. In each attack, the pain was localized to a region of one side of the head. Pain location varied between episodes in 12 patients. Pain quality was pressing, and pain intensity was mild to severe. There were no accompanying symptoms. Physical examination and all ancillary tests were unremarkable. Among seven patients who tried pharmacological treatments, one responded to antidepressants, another to indomethacin and three to other nonsteroidal anti-inflammatory drugs or simple analgesics. CONCLUSIONS: Paroxysmal pressing headache may be a new headache syndrome marked by short duration of the pain and shifting location.

Argyrophilic grain disease presenting as behavioral frontotemporal dementia.

Argyrophilic grain disease (AgD) is a frequent late-onset 4R tauopathy of old age characterized by the presence of profuse spindle-shaped argyrophilic grains (AGs). It is a neurodegenerative disorder that is clinically characterized by a slow progressive amnestic mild cognitive impairment similar to Alzheimer's disease. In rare instances, it is characterized as a behavioral-variant frontotemporal dementia (bv-FTD). In this study, we report a case with typical clinical and neuroimaging features of bv-FTD, who had autopsy findings consistent with a definitive diagnosis of AgD. We suggest that AgD might be included in the differential diagnosis of patients presenting with bv-FTD.
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Frontotemporal lobar degeneration: Study of a clinicopathological cohort.

Frontotemporal dementia results from different neurodegenerative diseases heterogeneous from a clinical, neuropathological and genetic point of view. Our main objective was to analyze the sociodemographic, clinical, neuropathological and molecular characteristics of cases with frontotemporal lobar degeneration from different Neurological Tissue Banks. FTD has been considered as a disease with onset below 65. However, diagnosis at higher ages is increasingly common. In our study, there was a correlation between symptoms and disease course with certain neuropathological diagnoses, with different distribution depending on age and sex. Combined pathology with Alzheimer's and vascular pathology was observed and presence of argyrophilic grains, with a different distribution in the different subgroups and a particular clinical and progression phenotype. Low percentage of APOE4 was detected. H1/H1 haplotype of the MAPT gene was the most frequent and appeared in relationship with 4R tauopathies. These results point to biologically significant differences between the different types of FTLD.

OnabotulinumtoxinA injections for atypical odontalgia: an open-label study on nine patients.

BACKGROUND: Atypical odontalgia (AO) manifests as continuous pain in the region of one or several teeth, in the absence of signs of dental pathology. Currently, there is insufficient evidence to establish treatment guidelines for AO. The aim of this study was to describe the effectiveness and safety of treatment with OnabotulinumtoxinA (OnabotA) on a series of patients with AO. METHODS: Nine patients with AO (four males and five females, aged between 31 and 77 years) received injections of OnabotA in the region of pain. The dosage used in each procedure ranged between 10 and 30 U, spread between 4 and 12 injection sites along the gums (n=9), the lips (n=3), and the hard palate (n=1). The median follow-up time was 27 months (interquartile range, IQR 20-40) and the median number of injection sessions per patient was seven (IQR 4.5-9). The assessment variables included the change in the maximal intensity of pain on a 0-10 numerical rating scale (NRS), the response latency, and the duration of the effect. RESULTS: All patients experienced a significant improvement, with ≥50% of reduction in the intensity of the maximal pain. The median of reduction of maximal pain after treatment was six points on the NRS (IQR 5-8.5). The response latency was 2-15 days and the duration of the effect was 2-6 months. No significant adverse reactions were registered. CONCLUSION: OnabotA may be a safe and effective option for the treatment of AO.

Argyrophilic Grain Pathology in Frontotemporal Lobar Degeneration: Demographic, Clinical, Neuropathological, and Genetic Features.

Frontotemporal lobar degeneration (FTLD) is a clinically, pathologically, and genetically heterogeneous group of disorders that affect the frontal and temporal lobes of the brain. FTLD classification distinguishes three main neuropathological groups: FTLD-tau, FTLD-TDP, and FTLD-FUS. As a four-repeat tauopathy, argyrophilic grain disease (AGD) is included in the FTLD-tau group. AGD may also appear in association with other neuropathological disorders. We describe the demographic, clinical, neuropathological, and genetic characteristics of a series of FTLD cases presenting with AGD. For this purpose, a clinico-pathological study of 71 autopsy-confirmed FTLD cases from different tissue banks was performed. AGD was found in 52.1% of FTLD cases. The presence of AGD increased with the increasing age (up to 88.9% in cases older than 80 years; p < 0.001) and was associated with higher ages at onset (p < 0.001) and death (p < 0.001). In AGD cases, progressive supranuclear palsy (PSP) was the most frequent clinical diagnosis (29.7%) and gait disturbance was the most common symptom (64.5%); behavioral and language symptoms were less frequent as compared with non-AGD cases (p = 0.055; p = 0.012). PSP was the most frequent neuropathological diagnosis among cases with AGD (32.4%). This group also showed less brain atrophy (p = 0.094) and higher prevalence of Alzheimer (p = 0.002) and vascular pathology (p = 0.047) as compared to the non-AGD group. We also observed that H1/H1 genotype was overrepresented in AGD cases (p = 0.018) and that there was no association with any specific APOE allele. A subanalysis of PSP cases according to the AGD status was carried out, yielding no significant differences.