Diagnosis of rare dementia syndromes: an algorithmic approach

The etiology of dementia can be diagnosed in most patients using a standard clinical approach consisting of physical, neurologic, and mental status examinations, and laboratory testing, lumbar puncture, and neuroimaging. In some cases, however, the clinical presentation or historical data are unusual, or the results of the workup are inconclusive or atypical. A rare cause of dementia may then be present and a complicated evaluation may be necessary to identify the specific disease process. A potentially useful approach to the diagnosis of rare dementing disorders consists of a series of diagnostic algorithms. This approach utilizes results of neuroimaging studies to guide the evaluation through additional diagnostic steps such as specific enzymatic or immunologic assays or biopsy of extraneural tissues. The disorders potentially detected by these algorithms typically have unusual clinical features such as early age of onset, abnormal neurologic signs and symptoms early in the clinical course, early personality and mood changes, extrapyramidal or cerebellar signs and symptoms, seizures, peripheral neuropathy or myopathy, and extraneural abnormalities involving the dermatologic, cardiovascular, musculoskeletal, or ocular systems. Accurate diagnosis of these rare causes of dementia is important for medical and psychiatric management, prognosis, and genetic counseling.     

Camptocormia or Pisa syndrome in multiple system atrophy

Although a mild stooped posture is a hallmark of parkinsonism, extreme trunk forward flexion is not common. This phenomenon was described in different etiological entities and called camptocormia. Other similar presentations called Pisa syndrome and antecollis were described mainly in extrapyramidal disorders. Authors present two cases of probable multiple system atrophy (MSA) with predominant parkinsonism and Pisa syndrome (or camptocormia). Both of them were previously misdiagnosed as idiopathic Parkinson's disease (PD) and one was reported 1 year earlier. The typical clinical presentation fulfilling the diagnostic criteria for multiple system atrophy, rapid progression with lack of responsiveness to L-DOPA and apomorphine and typical MRI putaminal pathology observed in both cases allowed us to make a diagnosis. Accuracy of clinical diagnosis in multiple system atrophy is still very poor. Therefore, unusual or rare clinical presentations may support the final diagnosis. The camptocormia, Pisa syndrome and antecollis may represent the continuum of the same motor phenomenon and most of the authors refer them to unusual form of axial dystonia. According to many clinical presentations on different forms of camptocormia/Pisa syndrome authors conclude that not etiology, but the localization of specific lesion, probably within putamen is responsible for that form of dystonia. In cases of parkinsonism and severe forward flexion of trunk multiple system atrophy, diagnosis should be considered.     

Is sphincter electromyography a helpful investigation in the diagnosis of multiple system atrophy? A retrospective study with pathological diagnosis

Sphincter electromyography (spEMG) is often used as an ancillary test when multiple system atrophy (MSA) is suspected. Our aim was to determine the clinical features associated with spEMG being performed, the influence of the result on the final clinical diagnosis, and its utility as a clinical investigation. A retrospective audit of all cases in the Queen Square Brain Bank between 1989 and 2002 was performed. The clinical features and diagnostic accuracy were compared between patients in whom spEMG was performed and those in whom it was not. From 845 sets of complete clinical records, we identified 37 (4.4%) cases that had been investigated with spEMG. Thirty of these cases had a pathological diagnosis of MSA. Of these 30, 24 had abnormal spEMGs, 5 had a borderline result, and only 1 had a normal spEMG. Sixty-six cases had pathologically proven MSA but no spEMG. Those investigated with spEMG were younger at disease onset (P < 0.001), more frequently male (P = 0.03), and more likely to have had other investigations performed. They had a greater incidence of pyramidal tract signs at final clinical diagnosis, and the final clinical diagnostic accuracy was higher (P = 0.04). Due to the retrospective nature of the study, balanced populations for calculation of sensitivity and specificity were not available. In this selected series of pathologically confirmed cases, investigation with spEMG was one of several factors associated with improved clinical diagnostic accuracy. A normal spEMG is unlikely in pathologically proven MSA, at least in cases with a mean symptom duration of more than 5 years when the test is performed.     

Congenital hypotonia: is there an algorithm?

This study was performed with the aim of determining the diagnostic profile of newborns with hypotonia and of analyzing the usefulness of different procedures in the diagnostic process. One hundred thirty-eight hypotonic newborns were identified through the search of hospital records in a 10-year period: 121 (88%) had central hypotonia and 13 (9%) had peripheral hypotonia, whereas 4 (3%) remained unclassified. Analysis of the contribution of clinical data and results of investigations led to the construction of an algorithm, by which all cases in the group were diagnosed. Step 1, which included clinical data and results of examinations, solved 50% of all diagnosed cases. Neuroimaging techniques made up step 2 and contributed to the diagnosis in 13%. Step 3 was accomplished by a search through Oxford Medical Databases, which yielded the final diagnosis in 9%, whereas karyotyping and fluorescent in situ hybridization for Prader-Willi syndrome comprised step 4 and contributed to the diagnosis in 6.5%. Biochemical tests formed step 5 and contributed to the diagnosis in 6%. Step 6, which included specific investigations of muscle and nerve, was diagnostic in 6%. The remaining cases (6.5%) were diagnosed only after several follow-up examinations. These results could assist the neonatologist when deciding the diagnostic approach to floppy newborns.     

A Case of Intradural-Extramedullary Form of Primary Spinal Cysticercosis Misdiagnosed as an Arachnoid Cyst

We describe a rare case of intradural-extramedullary primary spinal cysticercosis. A 42-year-old man visited our institute for lower back pain. He denied having consumed raw meet. Magnetic resonance (MR) images revealed an intradural pure cystic mass at the L3-L4 level. A radiologic diagnosis of spinal arachnoid cyst was established. Three years later, he complained of aggravated back pain, and follow-up MR examination showed a markedly expanded cyst, occupying the subarachnoid space from the T11 to the S1 level. L2 hemilaminectomy was performed, and a yellowish infected cyst bulged out through the dural opening. The cyst was removed en bloc. The histopathological findings of the cyst were consistent with parasitic infection. Serum enzyme-linked immunosorbent assay (ELISA) confirmed the presence of spinal cysticercosis. As there was no intracranial lesion, the final diagnosis was primary spinal cysticercosis, which is very rare. MR imaging is a sensitive diagnostic tool for detecting cystic lesions in the spine; however, it is difficult to distinguish cysticercosis from non-infectious cysts such as an arachnoid cyst without using gadolinium enhancement. Clinicians treating spinal cysts with an unusual clinical course should include cysticercosis as a differential diagnosis. We recommend contrast-enhanced MR imaging and serum ELISA in the diagnostic work-up of such cases.     

Peripheral nerves biopsies: analysis of 89 cases

Results of 89 peripheral nerve biopsies studied only by paraffin sections are analysed to determine the abnormalities incidence, and in what extent a general pathology laboratory can help in final diagnosis of patients with peripheral nerve disorders. 37% normal nerve biopsies and 63% with some histological alteration were found; only in 22% the nosological diagnosis was possible. A discussion about the low incidence of nosological diagnosis is made, and a literature revision on routine nerve biopsies. It is concluded that nerve biopsies should be done only in special cases, particularly when other diagnostic methods failed, taking into account always the limitation of the method, and preferentially studying a clinically involved nerve.     

Alzheimer's disease camouflaged by histrionic personality disorder

A common condition in Alzheimer's disease (AD) is unawareness of deficits. Different concepts try to elucidate the nature of this symptom. An essential question relates to the interaction of organic and psychogenic factors. Here we present a patient who displayed her cognitive deficits as attention-seeking behaviour. There was a history of histrionic personality disorder according to ICD-10 criteria. Unexpectedly, the final diagnosis after extensive diagnostic work-up was AD. The unusual coincidence of AD and a histrionic personality disorder hampered the clinical process of diagnosing dementia. We discuss unawareness as a complex concept incorporating neuroanatomical, psychiatric, and psychosocial aspects.     

Alzheimer's disease camouflaged by histrionic personality disorder

A common condition in Alzheimer's disease (AD) is unawareness of deficits. Different concepts try to elucidate the nature of this symptom. An essential question relates to the interaction of organic and psychogenic factors. Here we present a patient who displayed her cognitive deficits as attention-seeking behaviour. There was a history of histrionic personality disorder according to ICD-10 criteria. Unexpectedly, the final diagnosis after extensive diagnostic work-up was AD. The unusual coincidence of AD and a histrionic personality disorder hampered the clinical process of diagnosing dementia. We discuss unawareness as a complex concept incorporating neuroanatomical, psychiatric, and psychosocial aspects.     

Post-traumatic intracerebral hematoma

Fifty-five cases of post-traumatic intracerebral haematomas are analyzed, discussing the diagnostic value of such preliminary methods as plain skull films, EEG, echoencephalography. These methods, together with clinical findings make the diagnosis of intracerebral haematoma likely. The final diagnosis was based on carotid arteriography and computerized tomography of the brain, which provided additional information on traumatic brain damage. The diagnostic sensitivity of CT was higher. The considerable prognostic importance of the degree of consciousness disturbances and their duration is stressed. In the group of patients with lucidum intervallum the mortality was higher. Four patients were treated conservatively since CT demonstrated in them only small haematomas without displacement of the ventricles. The remaining patients were treated surgically removing the haematomas through craniotomy or craniectomy. In 54% of these cases improvement was obtained. The 33% mortality was moderate as compared with previous reports.     

The clinical utility of structural neuroimaging with MRI for diagnosis and differential diagnosis of dementia: a memory clinic study

OBJECTIVES: The individual contribution to the final comprehensive clinical diagnosis of neuropsychology (NP) and magnetic resonance imaging (MRI), respectively, was quantified in a specialized tertiary care setting to investigate the added clinical value of routine MRI. METHODS: In 106 patients referred to a university memory clinic for the work-up of cognitive disturbances the primary care diagnosis, the initial clinical neuropsychiatric diagnosis, the neuropsychological and MRI diagnoses, and the final comprehensive clinical diagnosis were documented. The neuropsychological investigation was performed using the CERAD test battery. MRI was performed using T1, double echo and FLAIR sequences without contrast medium. The change of the final comprehensive clinical diagnosis in relation to the initial neuropsychiatric diagnosis was used to determine the diagnostic contribution of both, MRI and NP. RESULTS: NP and MRI led to a significant change of the final comprehensive diagnosis in 26% of patients (CI: 0.26 +/- 0.09; p < 0.05). In addition, three cases of secondary dementias, and six cases of vascular encephalopathy without dementia were recognized by MRI. Sensitivity, specificity, and the positive predictive value were higher for NP and MRI, respectively, than for the initial clinical diagnosis alone. CONCLUSION: MRI as well as neuropsychological testing improves early detection and differential diagnosis of dementia and additionally supplies clinically relevant findings. MRI carries added clinical value in the investigation of dementias.     

Unusual clinical cases that mimic MS

Diseases which are associated with relapses and disability accumulation that mimic MS may be effectively treated if they are appropriately diagnosed. Unfortunately, however, it can be easy to assume that a patient is presenting with unusual symptoms of MS rather than establish unequivocally that there is no other cause. This article illustrates five short cases from a selection presented at the MS Forum Interactive Symposium at the LACTRIMS Congress, Brazil, 2004. These cases feature the differential diagnosis of MS and illustrate the importance of early and accurate diagnosis. Each case has clinical features suggestive of MS, together with diagnostic findings that are discordant with this disease. Clinical features that can easily be interpreted as unusual MS presentations, but which indicate the need to undertake additional investigation, are included.     

Factitious disorder by proxy: pediatric condition falsification

We present a comprehensive overview of the condition factitious disorder by proxy, also known as Munchausen syndrome by proxy. The review begins by highlighting essential definitions and the etiology and epidemiology of the disorder. It then analyzes relevant clinical issues such as assessment and diagnostic methods. The final section is a detailed discussion of the complex issues facing the clinician, including the process of confronting the perpetrator, relevant legal issues, and the treatment of the caretaker, child, and family through a multidisciplinary, team approach.     

Diagnostic approach to the congenital muscular dystrophies

Congenital muscular dystrophies (CMDs) are early onset disorders of muscle with histological features suggesting a dystrophic process. The congenital muscular dystrophies as a group encompass great clinical and genetic heterogeneity so that achieving an accurate genetic diagnosis has become increasingly challenging, even in the age of next generation sequencing. In this document we review the diagnostic features, differential diagnostic considerations and available diagnostic tools for the various CMD subtypes and provide a systematic guide to the use of these resources for achieving an accurate molecular diagnosis. An International Committee on the Standard of Care for Congenital Muscular Dystrophies composed of experts on various aspects relevant to the CMDs performed a review of the available literature as well as of the unpublished expertise represented by the members of the committee and their contacts. This process was refined by two rounds of online surveys and followed by a three-day meeting at which the conclusions were presented and further refined. The combined consensus summarized in this document allows the physician to recognize the presence of a CMD in a child with weakness based on history, clinical examination, muscle biopsy results, and imaging. It will be helpful in suspecting a specific CMD subtype in order to prioritize testing to arrive at a final genetic diagnosis.     

Clinical-radiological-anatomopathological correlations in cases of inoperable tumors

The analysis concerned 27 patients disqualified for radical surgical treatment and qualified for palliative procedures or conservative treatment in the Department of Neurosurgery, Medical Academy in Lód? in the years 1960-1976. The decisions of disqualification were based on the assessment of the clinical state, angiography of the cerebral vessels, pneumoencephalography or both these methods. Computer tomography was not available then, similarly as it is not available presently in most neurosurgical centres in Poland. The accuracy of the diagnosis of the nature of the pathological process and particularly its location based on these methods was compared with the results of postmortem examinations. The material was divided into two groups depending on the presence or absence of hydrocephalus. This division was based on the experiences showing that in cases with coexistent hydrocephalus paliative treatment is as a rule easier and more successful than similar treatment in cases without hydrocephalus. The analysis showed that two types of errors are possible when the possibilities of diagnostic investigations are at the level present in average neurosurgical centres in Poland. These errors may have a significant influence on the fates of the patients. The first type is due to erroneous estimation of the nature of the pathological process, with erroneous diagnosis of malignant process in cases without malignancy, and, conversely, diagnosis of non-malignant process in cases of malignant changes. Four such cases were found in this material. The second type of errors is due to false diagnosis of neoplasm location. Such errors lead to unsuccessful trials of radical treatment in cases with neoplasms situated in inaccessible sites or to unnecessary abandoning of surgical or palliative treatment in the presence of operable tumours. Both these types of errors are illustrated in the discussion.     

Accuracy of clinical diagnosis of progressive supranuclear palsy.

We assessed the accuracy of clinical diagnosis of progressive supranuclear palsy (PSP, Steele-Richardson-Olszewski disease) and the validity of existing sets of clinical diagnostic criteria for PSP (see Appendix) using neuropathologically examined cases from the Queen Square Brain Bank for Neurological Disorders. Diagnosis of PSP was made by 40 different physicians, and 60 cases clinically diagnosed as PSP when last assessed in life were studied. In 47 cases (78%), the diagnosis of PSP was confirmed pathologically. False-positive diagnoses included Parkinson's disease with significant additional cortical Lewy body (n = 3) or Alzheimer (n = 1) pathology, multiple system atrophy (n = 4), and corticobasal degeneration, Pick's disease, motor neurone disease, cerebrovascular disease, and a sporadic case of frontotemporal dementia and parkinsonism linked to chromosome 17 (1 case each). Most cases of PSP were diagnosed accurately by neurologists at the final assessment. Although application of National Institute of Neurological Disorders and the Society for PSP possible category marginally improved the accuracy of initial clinical diagnosis, none of the existing operational criteria could significantly improve accuracy of the final clinical diagnosis.     

Diagnostic accuracy of neurological problems in the emergency department

BACKGROUND: Previous studies describe significant rates of misdiagnosis of stroke, seizure and other neurological problems, but there are few studies examining diagnostic accuracy of all emergency referrals to a neurology service. This information could be useful in focusing the neurological education of physicians who assess and refer patients with neurological complaints in emergency departments. METHODS: All neurological consultations in the emergency department at a tertiary-care teaching hospital were recorded for six months. The initial diagnosis of the requesting physician was recorded for each patient. This was compared to the initial diagnosis of the consulting neurologist and to the final diagnosis, as determined by retrospective chart review. RESULTS: Over a six-month period, 493 neurological consultations were requested. The initial diagnosis of the requesting physician agreed with the final diagnosis in 60.4% (298/493) of cases, and disagreed or was uncertain in 35.7% of cases (19.1% and 16.6% respectively). In 3.9% of cases, the initial diagnosis of both the referring physician and the neurologist disagreed with the final diagnosis. Common misdiagnoses included neurocardiogenic syncope, peripheral vertigo, primary headache and psychogenic syndromes. Often, these were initially diagnosed as stroke or seizure. CONCLUSIONS: Our data indicate that misdiagnosis or diagnostic uncertainty occurred in over one-third of all neurological consultations in the emergency department setting. Benign neurological conditions, such as migraine, syncope and peripheral vertigo are frequently mislabeled as seizure or stroke. Educational strategies that emphasize emergent evaluation of these common conditions could improve diagnostic accuracy, and may result in better patient care.     

On clinical diagnosis of depression

In this paper, diagnosis of depression was deliberatively considered from a view of psychopathological studies, and problems of operational diagnostic system in psychiatry were discussed. For good clinical practices, 1) diagnosis must be considered as a part of clinical practices. 2) diagnosis must be closely related to therapeutic works, 3) the process of making a diagnosis itself should be managed to be remedial, and 4) a clinical category is expected to contain not only a summation of individual cases, and at the same time the link between the category and individual cases should not be abandoned. The author also discussed about some clinical maneuvers.     

Sensitivity of magnetoencephalography as a diagnostic tool for epilepsy: a prospective study

Aim. The diagnostic process for epilepsy can be lengthy and stressful, which may delay the start of treatment. The objective of this study was to determine the benefit of routine magnetoencephalography (MEG) with regard to diagnostic gain, compared to routine electroencephalography (EEG), EEG following sleep deprivation (EEGsd), and 24‐hour EEG. Methods. In this prospective study, patients were included from two centres (Academic Centre for Epileptology Kempenhaeghe, Heeze and Elisabeth‐Twee Steden Hospital, Tilburg) and MEG recording took place at a single centre (Amsterdam University Medical Centre, Vrije Universiteit Amsterdam) in The Netherlands. Consecutively referred patients from peripheral hospitals were included between August 2013 and March 2016. Patients were offered routine MEG in addition to EEG examination and MRI for the diagnosis of epilepsy. The final clinical diagnosis was based on all available clinical data and test results at the end of the diagnostic process. Sensitivity, specificity, and positive and negative predictive values were calculated for routine EEG, routine EEG plus additional EEG and MEG. In addition, diagnostic gain associated with MEG, relative to the other modalities, was calculated. Secondary outcome was congruence of localization of epileptiform discharges between MEG and MRI or final clinical diagnosis. Results. Based on a cohort of 138 patients, sensitivity and specificity was shown to be 31.6% and 78.4% for routine MEG, 31.6% and 100% for routine EEG, and 52.6% and 97.3% for routine EEG plus additional EEG, respectively. Routine MEG demonstrated a diagnostic gain of 16.8% compared to routine EEG and 9.5% compared to routine EEG plus additional EEG. In 35.7% of patients with a lesion on MRI that was consistent with the final clinical diagnosis, MEG showed epileptiform discharges in the same area. Conclusion. Routine MEG may provide additional value during the initial diagnosis of epilepsy.     

Presymptomatic Parkinson's disease: the Arizona experience

There is a growing interest in presymptomatic diagnosis of Parkinson's disease (PD), but the best and most practical method to screen and confirm asymptomatic individuals for PD needs further study. The Banner-Sun Health Brain and Body Donation program in Sun City, Arizona has studied primarily PD and Alzheimer's disease. Enrollees receive annual prospective standardized evaluation that includes clinical, biomarker testing, and at autopsy, neuropathological examination is performed followed by a consensus conference that determines final diagnosis. Since numerous Controls receive these assessments, these subjects become an excellent cohort to study presymptomatic PD. We found that Controls with partial diagnostic criteria for PD (1 of either rest tremor or bradykinesia) had a 6.6 relative risk for eventually developing full diagnostic criteria for PD. Neuropathologic examination has uncovered cases of "incidental Lewy body disease" (ILBD). We have shown that ILBD cases during life demonstrated no significant differences in clinical assessment versus similarly assessed controls. However, electrophysiological assessment showed subclinical low frequency rest discharges in some ILBD cases. Electroencephalography spectral frequency of ILBD cases was lower than for controls but not as low as for PD cases. The longitudinal assessments of this brain bank offer significant opportunities for the study of presymptomatic PD.     

Informativeness of structured diagnostic interviews in the identification of Tourette's disorder in referred youth

Although specialized programs have greatly advanced the treatment of youth with Tourette's disorder (TD), not all children with TD reach such programs, raising questions as to whether TD is adequately identified outside specialized settings. There is thus a need for evidence that cases identified in the nonspecialty setting are "true cases." Because structured diagnostic interview methodology can reduce errors of omission, this approach can facilitate the identification of TD in referred youth outside specialized programs. Similarities between cases ascertained in specialty and nonspecialty settings would suggest that those identified in the nonspecialty setting were indeed "true cases." Comparisons were made between youth with TD ascertained through a specialized TD program who had both a structured diagnostic interview-derived diagnosis of TD plus an expert evaluation of TD (N = 103), with youth ascertained through a non-TD specialized pediatric psychopharmacology program who had a structured diagnostic interview-derived diagnosis of TD (N = 92). Irrespective of ascertainment source, children with structured interview-derived diagnosis of TD shared similar correlates in terms of tic severity, mean age of onset and duration of tics, as well as patterns of comorbidity well known to be associated with TD in clinical samples. Children meeting diagnostic criteria for TD on structured diagnostic interviews share similarities and patterns of clinical correlates, irrespective of ascertainment through a specialized TD or non-TD specialized clinic. These findings support the usefulness of structured diagnostic interview methodology as a diagnostic aid for the identification of TD in non-TD specialized settings and facilitate delineation of patterns of comorbidity.