J Haan

Leiden University Medical Centre, Leyden, South Holland, Netherlands

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Publications (240)1279.44 Total impact

  • Cephalalgia 04/2015; DOI:10.1177/0333102415580111 · 4.12 Impact Factor
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    ABSTRACT: Cluster headache is a severe neurological disorder with a complex genetic background. A missense single nucleotide polymorphism (rs2653349; p.Ile308Val) in the HCRTR2 gene that encodes the hypocretin receptor 2 is the only genetic factor that is reported to be associated with cluster headache in different studies. However, as there are conflicting results between studies, we re-evaluated its role in cluster headache.
    Cephalalgia 11/2014; DOI:10.1177/0333102414557839 · 4.12 Impact Factor
  • Neurology 06/2014; DOI:10.1212/WNL.0000000000000590 · 8.30 Impact Factor
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    ABSTRACT: CADASIL is an autosomal dominant inherited disease, characterized by mid-adult onset of cerebrovascular disease and dementia. CADASIL is caused by mutations in the NOTCH3 gene, which encodes the NOTCH3 protein. Pathogenic mutations in CADASIL are highly distinctive in the sense that they lead to the loss or gain of a cysteine residue in 1 of the 34 EGFr domains of the NOTCH3 protein. The majority are missense mutations, but small deletions, insertions and splice-site mutations have been reported, which typically also lead to a numerical cysteine alteration. Whether numerical cysteine-altering mutations are a rule in CADASIL remains subject of debate, as there are reports suggesting pathogenicity of other types of mutations. However, for most of these the association with CADASIL was later revoked or is questionable. Here, we discuss and provide recommendations for the interpretation of NOTCH3 mutations in the diagnosis of CADASIL.
    Expert Review of Molecular Diagnostics 06/2014; 14(5):593-603. DOI:10.1586/14737159.2014.922880 · 4.27 Impact Factor
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    ABSTRACT: Abstract Hereditary cerebral hemorrhage with amyloidosis - Dutch type is an autosomal dominant hereditary disease caused by a point mutation in the amyloid precursor protein gene on chromosome 21. The mutation causes an amino acid substitution at codon 693 (E22Q), the 'Dutch mutation'. Amyloid beta, the product after cleavage of the amyloid precursor protein, is secreted into the extracellular space. The Dutch mutation leads to altered amyloid beta cleavage and secretion, enhanced aggregation properties, higher proteolysis resistance, lowered brain efflux transporter affinity, and enhanced cell surfaces binding. All these result in amyloid beta accumulation in cerebral vessel walls, causing cell death and vessel wall integrity loss, making cerebral vessel walls in hereditary cerebral hemorrhage with amyloidosis-Dutch type more prone to rupture and obstruction, leading to hemorrhages and infarcts. Studying the effects of altered amyloid beta metabolism due to mutations like the 'Dutch' provides us with
    Reviews in the neurosciences 05/2014; DOI:10.1515/revneuro-2014-0008 · 3.31 Impact Factor
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    ABSTRACT: Hemiplegic migraine (HM) and alternating hemiplegia of childhood (AHC) are rare episodic neurological brain disorders with partial clinical and genetic overlap. Recently, ATP1A3 mutations were shown to account for the majority of AHC patients. In addition, a mutation in the SLC2A1 gene was reported in a patient with atypical AHC. We therefore investigated whether mutations in these genes may also be involved in HM. Furthermore, we studied the role of SLC2A1 mutations in a small set of AHC patients without ATP1A3 mutations. We screened 42 HM patients (21 familial and 21 sporadic patients) for ATP1A3 and SLC2A1 mutations. In addition, four typical AHC patients and one atypical patient with overlapping symptoms of both disorders were screened for SLC2A1 mutations. A pathogenic de novo SLC2A1 mutation (p.Gly18Arg) was found in the atypical patient with overlapping symptoms of AHC and hemiplegic migraine. No mutations were found in the HM and the other AHC patients. Screening for a mutation in the SLC2A1 gene should be considered in patients with a complex phenotype with overlapping symptoms of hemiplegic migraine and AHC.
    Cephalalgia 05/2014; DOI:10.1177/0333102414532379 · 4.12 Impact Factor
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    ABSTRACT: Familial hemiplegic migraine (FHM) is a rare monogenic subtype of migraine with aura, characterized by motor auras. The majority of FHM families have mutations in the CACNA1A and ATP1A2 genes; less than 5% of FHM families are explained by mutations in the SCN1A gene. Here we screened two Spanish FHM families for mutations in the FHM genes. We assessed the clinical features of both FHM families and performed direct sequencing of all coding exons (and adjacent sequences) of the CACNA1A , ATP1A2 , PRRT2 and SCN1A genes. FHM patients in both families had pure hemiplegic migraine with highly variable severity and frequency of attacks. We identified a novel SCN1A missense mutation p.Ile1498Met in all three tested hemiplegic migraine patients of one family. In the other family, novel SCN1A missense mutation p.Phe1661Leu was identified in six out of eight tested hemiplegic migraine patients. Both mutations affect amino acid residues that either reside in an important functional domain (in the case of Ile(1498)) or are known to be important for kinetic properties of the NaV1.1 channel (in the case of Phe(1661)). We identified two mutations in families with FHM. SCN1A mutations are an infrequent but important cause of FHM. Genetic testing is indicated in families when no mutations are found in other FHM genes.
    Cephalalgia 04/2014; DOI:10.1177/0333102414529195 · 4.12 Impact Factor
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    ABSTRACT: Familial hemiplegic migraine (FHM) is a rare monogenic subtype of migraine with aura that includes motor auras. Prophylactic treatment of FHM often has marginal effects and involves a trial-and-error strategy based on therapeutic guidelines for non-hemiplegic migraine and on case reports in FHM. We assessed the response to prophylactic medication in an FHM family and sequenced the FHM2 ATP1A2 gene in all available relatives. A novel p.Met731Val ATP1A2 mutation was identified. Attack frequency was reduced significantly with sodium valproate monotherapy ( N = 1) and attacks ceased completely with a combination of sodium valproate and lamotrigine ( N = 2). We report dramatic prophylactic effects of sodium valproate and lamotrigine in an FHM2 family, making these drugs worth considering in the treatment of other FHM patients.
    Cephalalgia 01/2014; DOI:10.1177/0333102413520086 · 4.12 Impact Factor
  • Joost Haan, Peter J Koehler
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    ABSTRACT: There have been many descriptions of presumed 'hysterics' in fiction, many appearing in French literature, but also in a number of other languages. It is clear that contemporary medical ideas and insights about hysteria had a major influence on its depiction in novels. This is particularly true for naturalistic literature, which has been the subject of previous reviews. Here, we focus on a more recent novel: Human Traces by Sebastian Faulks (2005). What is special about the depiction of hysteria in this work is that the presumed 'hysteric' turns out not to be hysteric at all. In the novel, as well as in this chapter, the diagnosis of hysteria is discussed in the light of theories about hysteria of around 1900. For comparison, we present some examples of true 'hysterics' as they occur in fiction. Since it has become clear that severe nonpsychiatric diseases such as an ovarian teratoma can lead to bizarre phenotypes, the association of 'hysteria' with the womb has to be seen in another light. © 2014 S. Karger AG, Basel.
    Frontiers of neurology and neuroscience 01/2014; 35:99-108. DOI:10.1159/000360063
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    ABSTRACT: Headache and epilepsy often co-occur. Epidemiologic studies conducted in the past few years reinforce the notion of a bi-directional association between migraine and epilepsy. Data on an association between headache (in general) and epilepsy, however, are less clear. Peri-ictal headache often presents with migraine-like symptoms and can be severe. A correct diagnosis and management are paramount. It was demonstrated that cortical hyperexcitability may underlie both epilepsy and migraine. A recent study linked spreading depolarisation, the supposed underlying pathophysiological mechanism of migraine with aura, to epilepsy. Although this study was carried out in patients who had suffered a subarachnoid haemorrhage, the finding may shed light on pathophysiological mechanisms common to epilepsy and migraine.
    Current Pain and Headache Reports 08/2013; 17(8):351. DOI:10.1007/s11916-013-0351-x · 2.26 Impact Factor
  • Journal of Neurology 07/2013; 260(8). DOI:10.1007/s00415-013-7050-8 · 3.84 Impact Factor
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    ABSTRACT: BACKGROUND: About 10% of cluster headache patients have the chronic form. At least 10% of this chronic group is intractable to or cannot tolerate medical treatment. Open pilot studies suggest that occipital nerve stimulation (ONS) might offer effective prevention in these patients. Controlled neuromodulation studies in treatments inducing paraesthesias have a general problem in blinding. We have introduced a new design in pain neuromodulation by which we think we can overcome this problem. METHODS/DESIGN: We propose a prospective, randomised, double-blind, parallel-group international clinical study in medically intractable, chronic cluster headache patients of high- versus low-amplitude ONS. Primary outcome measure is the mean number of attacks over the last four weeks. After a study period of six months there is an open extension phase of six months. Alongside the randomised trial an economic evaluation study is performed. DISCUSSION: The ICON study will show if ONS is an effective preventive therapy for patients suffering medically intractable chronic cluster headache and if there is a difference between high- and low-amplitude stimulation. The innovative design of the study will, for the first time, assess efficacy of ONS in a blinded way.
    Cephalalgia 05/2013; 33(15). DOI:10.1177/0333102413490351 · 4.12 Impact Factor
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    ABSTRACT: To determine the prevalence and nature of trigeminal neuralgia in a large group of cluster headache patients. Cluster-tic syndrome is a rare headache syndrome in which trigeminal neuralgia and cluster headache co-occur. The existence of cluster-tic syndrome as a separate entity is questioned, and figures on prevalence of simultaneous existence of cluster headache and trigeminal neuralgia are not available. As part of a nationwide study on headache mechanisms in cluster headache (Leiden University Medical Centre Cluster headache Neuro Analysis programme), we collected clinical data of 244 cluster headache patients using a semistructured telephone interview in a cross-sectional design. In 11 (4.5%) cluster headache patients, attacks fulfilling International Headache Society criteria for trigeminal neuralgia were also present. In all cases, trigeminal neuralgia occurred ipsilateral to cluster headache and in the majority (82%) in the ophthalmic branch. In 8 of these 11 patients (73%), the frequency and time pattern of trigeminal neuralgia seemed to parallel cluster headache and was likely a part of the cluster headache spectrum. In the 3 remaining patients, cluster headache and trigeminal neuralgia were unrelated in time and appeared to occur independently. Trigeminal neuralgia co-occurred in 11/244 (4.5%) of cluster headache patients. In only 3 (1.2%) patients, trigeminal neuralgia seemed to occur independently from cluster headache episodes. Trigeminal neuralgia (-like) attacks in cluster headache patients are most of the time part of the cluster headache spectrum and should then probably not be treated separately. A shared underlying pathophysiological mechanism of cluster headache and trigeminal neuralgia is not supported by this study.
    Headache The Journal of Head and Face Pain 05/2013; 53(8). DOI:10.1111/head.12161 · 3.19 Impact Factor
  • Joost Haan
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    ABSTRACT: In the gangster movie White Heat, the main character, Cody (played by James Cagney), suffers from 2 headache attacks. Here, I analyze these attacks by using the International Headache Society criteria, but an unequivocal diagnosis is not possible. Nevertheless, the attacks play an important role in the narrative and - as representation of something between "real" (mimesis) and not real - provide a ground for reflection on how to think of headache in general.
    Headache The Journal of Head and Face Pain 04/2013; 53(6). DOI:10.1111/head.12122 · 3.19 Impact Factor
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    ABSTRACT: BACKGROUND: Cluster headache (CH) is a primary headache disorder that is diagnosed based on the patient's history. For large-scale epidemiologic and genetic studies, a web-based, preferably short, questionnaire can be a feasible alternative to replace time-consuming clinical interviews. METHODS: Self-reported CH patients were enrolled via our research website. Participants meeting screening criteria were directed to the Leiden University Cluster headache Analysis program (LUCA) questionnaire. Individual diagnoses were calculated using an algorithm based on International Headache Society criteria. Subsequently, semi-structured telephone interviews were carried out to validate the LUCA questionnaire. The shorter Quick Ascertainment of Cluster Headache (QATCH) questionnaire for diagnosing CH was constructed by using logistic regression to select the most predictive questions. RESULTS: Via our website 437 self-reported CH patients were recruited. Of these, 291 patients were included in this cross-sectional study. The LUCA questionnaire was valid and accurate. Using logistic regression, three questions (QATCH) provided similar sensitivity (53.8% vs. 57.2%), specificity (88.9% vs. 87.5%), positive predictive value (95.5% vs. 95.9%) and negative predictive value (30.8% vs. 28.8%) compared with the LUCA questionnaire. CONCLUSION: The web-based LUCA questionnaire was accurate and reliable in diagnosing CH among self-reported patients. Males with headache attacks of short duration and long headache-free intervals (months to years) are very likely to have CH.
    Cephalalgia 04/2013; 33(11). DOI:10.1177/0333102413479835 · 4.12 Impact Factor
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    ABSTRACT: To describe the prevalence of aura in a Dutch cluster headache (CH) population. Cross-sectional, epidemiological study. As part of a large-scale study into headaches conducted in Leiden (the Netherlands), patients experiencing headaches were identified by means of questionnaires on a headache website. One group of patients with CH was approached by telephone and an interview on aura-related symptoms was performed by means of a standardized questionnaire. The presence of migraine co-morbidity was also investigated. Of the interviewed CH patients, 22 out of 244 (9.0%) had aura-related symptoms preceding a CH attack, which were predominantly visual in nature. The majority (72.7%) of these patients did not have migraine co-morbidity. Aura-related symptoms can occur in CH without migraine co-morbidity. In clinical practice, it should be taken into account that the presence of an aura does not always indicate migraine.
    Nederlands tijdschrift voor geneeskunde 01/2013; 157(1):A5306.
  • Joost Haan
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    ABSTRACT: The metaphors of migraine make it a challenging source of inspiration for writers of fiction. The visual aura is a hallucination, the outside world - the so-called 'reality' - is distorted. The excruciating pain can stand for horror, punishment, and fate. Photophobia, phonophobia, and osmophobia underline visual, acoustic, and olfactoric stimuli. The protagonist sees, hears, and smells more, but not always better. Paradoxically, this increased awareness of 'reality' results in a need to seek isolation. Often, the end of a migraine attack is like a rescue. Immediately after an attack the fear of the next one begins. As migraine is hereditary, there are also aspects of solidarity, but shame and blame are nearby.
    Monographs in neural sciences 01/2013; 31:126-36. DOI:10.1159/000343255
  • Joost Haan
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    ABSTRACT: Parkinson's disease is a complex disorder with many fascinating features. Its onset is creeping, the progression is slow but inevitable. There are motor symptoms, such as a tremor, rigidity, bradykinesia, mask-like facial expression, and postural abnormalities, but also hallucinations, cognitive deterioration, and depression. In many novels, fictive patients with Parkinson's disease play a role. It seems that authors have used many aspects of the disease to emphasize their messages. Their narratives include themes such as rigidity, petrifaction, confusion, dementia, and hallucinations. In this chapter, as examples, several protagonists with Parkinson's disease will be described from works of John Updike, Jonathan Franzen, Sue Miller, J.M. Coetzee, and John Harding, among others.
    Monographs in neural sciences 01/2013; 31:178-87. DOI:10.1159/000343237
  • Joost Haan
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    ABSTRACT: Protagonists who are locked-in can be found throughout fiction, probably because being locked-in serves as a strong philosophical metaphor for human existence. In this chapter, three protagonists who are locked-in due to physical/medical reasons will be described. The fictitious stories of Noirtier from The Count of Monte Cristo by Alexandre Dumas and that of Madame Raquin from Thérèse Raquin by Émile Zola are followed by the real-life story of Jean-Dominique Bauby's The Diving Bell and the Butterfly. Dumas' Noirtier is considered the first description of the locked-in syndrome in literature, and Madame Raquin appears to be locked-in also, but her description leaves many questions. Bauby's autopathography is chosen from many several similar discourses as it contains cross-references to Noirtier, Dumas' prototype of the syndrome, but also because it is of high literary value. The similarities and remarkable differences between these three case reports of this existentialistically important state of being will be highlighted, with an emphasis on the focus of their narratives.
    Progress in brain research 01/2013; 206:19-34. DOI:10.1016/B978-0-444-63364-4.00018-1 · 5.10 Impact Factor
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    ABSTRACT: OPINION STATEMENT: Hemiplegic migraine (HM) is a rare subtype of migraine with aura, characterized by transient hemiparesis during attacks. Diagnosis is based on the International Classification of Headache Disorders criteria (ICHD-II). Two types of HM are recognized: familial (FHM) and sporadic hemiplegic migraine (SHM). HM is genetically heterogeneous. Three genes have been identified (CACNA1A, ATP1A2, and SCN1A) but more, so far unknown genes, are involved. Clinically, attacks of the 3 subtypes cannot be distinguished. The diagnosis can be confirmed but not ruled out by genetic testing, because in some HM patients other, not yet identified, genes are involved. The presence of additional symptoms (such as chronic ataxia or epilepsy) may increase the likelihood of identifying a mutation. Additional diagnostics like imaging, CSF analysis, or an EEG are mainly performed to exclude other causes of focal neurological symptoms associated with headache. Conventional cerebral angiography is contraindicated in HM because this may provoke an attack. Because HM is a rare condition, no clinical treatment trials are available in this specific subgroup of migraine patients. Thus, the treatment of HM is based on empirical data, personal experience of the treating neurologist, and involves a trial-and-error strategy. Acetaminophen and NSAIDs often are the first choice in acute treatment. Although controversial in HM, triptans can be prescribed when headaches are not relieved sufficiently with common analgesics. An effective treatment for the severe and often prolonged aura symptoms is more warranted, but currently no such acute treatment is available. Prophylactic treatment can be considered when attack frequency exceeds 2 attacks per month, or when severe attacks pose a great burden that requires reduction of severity and frequency. In no strictly preferred order, flunarizine, sodium valproate, lamotrigine, verapamil, and acetazolamide can be tried. While less evidence is available for prophylactic treatment with topiramate, candesartan, and pizotifen, these drugs can also be considered. The use of propranolol in HM is more controversial, but evidence of adverse effects is insufficient to contraindicate beta-blockers.
    Current Treatment Options in Neurology 12/2012; 15(1). DOI:10.1007/s11940-012-0208-3 · 2.18 Impact Factor

Publication Stats

7k Citations
1,279.44 Total Impact Points


  • 1987–2015
    • Leiden University Medical Centre
      • • Department of Neurology
      • • Department of Human Genetics
      • • Department of Clinical Genetics
      Leyden, South Holland, Netherlands
  • 1996–2014
    • Rijnland Hospital, Leiderdorp
      Лейдердорпе, South Holland, Netherlands
  • 1990–2013
    • Leiden University
      Leyden, South Holland, Netherlands
    • University of Antwerp
      Antwerpen, Flanders, Belgium
  • 2010
    • Canisius-Wilhelmina Ziekenhuis
      Nymegen, Gelderland, Netherlands
  • 2006
    • Medisch Centrum Haaglanden
      's-Gravenhage, South Holland, Netherlands
  • 1994
    • University of Amsterdam
      • Department of Psychiatry
      Amsterdamo, North Holland, Netherlands
  • 1992
    • Academic Medical Center (AMC)
      Amsterdamo, North Holland, Netherlands
  • 1991
    • Medisch Centrum Leeuwarden
      Leewarden, Friesland, Netherlands