A Case Study Tutorial for
Computer-Assisted Diagnostic Checklist
As literature continues to amass at an ever increasing rate so too does the demand for more intelligent information systems to manage it. Current information systems return journal citations or clinical summary titles and are not designed to generate diagnostic lists. Considering computers are more efficient at processing large amounts of information than the human brain, speaks to the need to explore computer-assisted diagnostic approaches. The checklist concept, well established in industry, has had a limited role in medicine, of which only a small part relates to diagnosis. Because checklists outperform physician recall, an effort to implement intelligent systems that utilize computer-assisted diagnostic checklists, may enhance physician performance at point of care. We here consider the applicability and efficacy of two diagnostic checklist programs.
Logic of CHECKLIST
“Multiple choice” question vs. “Fill in the blank”
Result: Higher success rate when cued w/ choices
In an attempt to cope with the increasing complexity of disease and difficulty in managing clinical information in neurology two checklist programs, NeurologicDx (3) and NeurologyINDEX (4) were developed. In the context of case vignettes, we demonstrate the concept of a diagnostic checklist in clinical neurology.
When you don’t know what you don’t know, you think you know everything, as such checklists can make you aware of what you are not aware of. It is for rare, uncommon or complex neurologic conditions, where diagnosis may be problematic, that the programs considered here are most helpful in assisting with diagnosis and potentially reducing diagnostic error.
Developing specialty specific systems is important as this helps maintain checklist relevance and length. A proprietary key term tagging system and advanced algorithms generate the checklists for the programs described. The programs under discussion can be used together or independently, with NeurologicDx designed for multi-term input and NeurologyINDEX for single term application. On screen tutorial is available for each program.
Case 1 and 2 are Massachusetts General Hospital Case Records 3-2010 and 13-2012 (8, 9). Both cases illustrate the use of a single term search. The first uses a neuroimaging feature from the case history, the second a key term from the title of the case record. In case 1, using NeurologyINDEX, in a rare, seaming complex case, the diagnosis of Krabbe’e disease is listed among a 19 item checklist, from the search of a single MR imaging feature “enlarged optic nerve”. In the clinical context of the case history, Krabbe’s disease was the most likely of the diagnoses listed. A link to Krabbe’s disease generates a “key term profile” for this disease. In case 2, using NeurologyINDEX, a single term “jaundice” selected from the title of the case record, generates a neurologically focused diagnostic checklist that includes “pernicious anemia”, the diagnosis in this case. Knowing the clinical context of the case, in conjunction with the fact this is a specialty database, focuses the diagnostic considerations in the checklist. The inclusion of pernicious anemia prompts the user to consider a condition that otherwise might be overlooked. In Case2 using a multi-term diagnostic search with “jaundice” and “weight loss” in NeurologicDx a more restricted diagnostic list is shown, still with pernicious anemia included.
Selecting valid and unique key term(s) determines the quality of the diagnostic considerations generated. Anywhere from one to three terms work best depending on key term uniqueness. The more unique the term the fewer the terms needed. In case 4 where the diagnosis was delayed using the traditional approach, three somewhat non-specific but valid key terms were entered in NeurologicDx. Trying different three term combinations and surveying the resulting lists for additional diagnostic entities can be an effective strategy. Using NeurologyINDEX to compile a disease profile for a given disease or list of diseases for a given sign, symptom or key term, and NeurologicDx, to generate differential diagnostic lists from one or more signs, symptoms or key terms allows for dynamic indexing of neurologic disease heretofore not possible. (see Diagnostic Approach In Neurology pg.iii)
While recall works best for simple cases, checklists, as pneumonic tools, outperform physician recall for diagnosis in more difficult cases (7). The programs described here are not meant to “automate diagnosis”, but rather be used by neurologists in the context of a given patient’s neurologic illness, when diagnosis is problematic, to broaden the diagnostic considerations at point of care. In the vast majority of cases the first approach to diagnosis should be to use traditional methods, followed by a computer-assisted program when the degree of difficulty exceeds that which traditional methods are capable.
Tutorials for NeurologicDx and NeurologyINDEX are available at the respective websites (3, 4).
While Google and other search engines do remarkably well at retrieving citations and associating specific term(s), they lack the ability to compile diagnostic checklists. It’s here with the use of intelligent information systems that use ”smart algorithms”, that NeurologicDx and NeurologyINDEX can transform information into a more relevant usable diagnostic format.
Information has increased 10 fold in the past 50 years and continues to increase exponentially. Solving the information problem by increasing CME demands is analogous to trying to juggle more balls knowing the human limit has been reached.
It’s time to replace outdated strategies with creative solutions, not adding more ineffective requirements. Diagnostic checklists are a step that direction.
NeurologicDX & NeurologyINDEX
Diagnostic checklist at point of care
Because Checklists outperform physical recall
- Indexed by 20,000 signs, symptoms, key terms and diseases.
- Dynamic checklist for rapid access to specific referenced information.
- Differential diagnosis at point of care for single symptom.
- Profile for selected disease.
- Continuous updates — most current resource in clinical neurology.
- Indispensable resource for residents and practicing neurologists.
- Specialty specific — Neurology.
- Access whenever, wherever with your preferred handheld device or PC.
- Open access on the internet.
NeurologicDx.com and NeurologyINDEX.com are diagnostic tools that provide dynamic and comprehensive differential diagnostic checklists not available elsewhere.
The use of advanced search algorithms to provide valid extrapolated diagnostic considerations, an augmented intelligence, is a unique feature note shared by other systems. Recent study shows neurologists can realize a substantial increase in differential diagnostic capability using computer generated checklists.
Because checklists outperform physician recall, an effort to implement intelligent systems as NeurologyINDEX.com and NeurologicDx.com, that utilize diagnostic checklist, should be promoted with the aim of enhancing physician performance with mobile devices at point of care.
- Gawande A. The Checklist Manifesto – How to get things right. New York, NY Metropolitan book, 2009.
- Ely JW, Graber ML, Crosberry P. Checklists to reduce diagnostic error. Acad Med 2011; 86: 307-313.
- www.NeurologicDx.com 2.0 open access database 2015.
- www.NeurologyINDEX.com 1.0 open access database 2015
- Chabris C and Simons D. The Invisible Gorilla, How our intuitions deceive us. New York, NY, Random house Inc., 2010.
- Haynes AB, Weiser TG, Berry WR, et al. A surgical safety checklist to reduce morbidity and mortality in a global population. New Engl J Med 2009; 360: 491-499.
- Finelli PF, McCabe AL. Computer generated checklist significantly improves differential diagnosis in neurologic disease over simple recall. Neurol (abstract). 2014; 82: Suppl (P1.319).
- Case Records of the Massachusetts General Hospital (Case record 3-2010) New Engl J Med 2010; 362; 346-356.
- Case Records of the Massachusetts General Hospital (Case record 13-2012) New Engl Med 2012; 366; 1226-1236.
- Stephen CD, Saper CB, Samuels MA. Clinical Case Conference: A 41-Year-Old Women with Progressive Weakness and Sensory Loss. Ann Neurol 2014; DOI; 10.1002/ana.24072
Diagnostic Approach in Neurology
The diagnosis begins with collecting information usually from the patient or other informant about the patient, as well as results from laboratory and/or neuroimaging studies. Aspects as the timing, progression, and exacerbating or mitigating circumstances regarding the symptoms all figure prominently in arriving at the diagnosis. In the end, scores of pieces of information will be processed to formulate a diagnosis. Factored into the process will be your knowledge of the patients clinical symptoms and your practice experience. Occassionily doctors come across patients whose condition presents difficulty in diagnosis, whether it be a rare condition, uncommon presentation of a common disease or other cause. In these cases where traditional diagnostic methods fall short the approach may involve a diagnostic search.
Fundamental to being a good diagnostician is the ability to concisely summarize the essential elements of a case. It’s this same skill set that allows the clinician to distill out the key terms essential in the diagnostic search, and used in those 20% of cases where diagnosis is difficult and illusive.
The proper selection of key terms cannot be overemphasized, particularly as they apply to the diagnostic search as described in the case vignettes that follow. As will be shown, the validity and uniqueness of the search term is paramount and determine which and how many terms will be used in the search.
We illustrate how difficult problems can be approched and solved with proper key term seletion. The number of terms most frequently is 1 or 2 if unique (as with Cases 2, 3, 5, 6) and less often 3 and rarely 4 for valid but non-specific terms (as with Cases 4). In the cases that follow two diagnostic search programs NeurologyINDEX, for single term entry and NeurolgicDx, for multiterm entry, will be demonstrated and sometimes employed in tandem in the same case vignette (as with Case 5).
Remember, the magic of the diagnostic search is overwhelmingly dependent on key term selection. Your ability to appreciate this concept and develop the skill for key term selection largely determines the success or failure of your diagnostic search.
In the cases that follow you will see how as few as one or two properly selected terms can generate checklists and suggest diagnoses not considered by more senior physicians because they fail to utilize computer-assisted diagnostic aides or master the skill of key term selection.
1. Krabbe’s disease [S]
A 5 month-old-boy was seen for developmental delay. Examination showed hyperactive deep tendon reflexes and bilateral Babinski sign. MR imaging showed increased signal of deep white matter on T2W image sequence and an enlarged optic chiasm and optic nerves.
Search strategy: On the basis of a single valid and somewhat unique neuroimaging finding “enlarged optic nerve”, a diagnostic search was done using NeurologyINDEX.
Comments: In a rare seemingly complex case, the diagnosis of Krabbe’s diasease is listed among a 19 item checklist from the search of a single MR imaging feature “enlarged optic nerve”. In the clinical context of the case, Krabbe’s disease was the most likely of the conditions listed.
Selecting Krabbe’s from the list for an additional search with NeurologyINDEX, generates a “key term profile”, for this disease entity, as shown in the following result list.
2. Pernicious anemia [S, M]
A 62-year-old-man presented with a 4 month history of paresthesias, weight loss, jaundice and anemia and a non-focal neurologic examination(9).
Search strategy: In this case, using NeurologyINDEX, a single term “jaundice” selected from the title of the Case Record was used.
Comments: Knowing the clinical context of the case in conjunction with the fact this is a specialty database, searching on “jaundice” generates a diagnostic checklist that includes, “pernicious anemia”, the diagnosis in this case. Seeing pernicious anemia listed prompts the user to consider a condition that otherwise might be overlooked. Clicking on pernicious anemia opens citation and key term profile for that disease (see right side of above panel).
Search strategy: Alternatively two terms “jaundice” and “weight loss” can be used in a diagnostic search with NeurologicDx.
Comment: In NeurologicDx multiple terms that are valid, yet at a minimum, reduce the differential checklist considerations considerably and include both B12 deficiency and pernicious anemia among the 8 choices. This example contrasts a single versus multiple term entry in the two diagnostic systems noting different results but the correct diagnosis is present in both lists. Above is shown title page and conclusion of New England Journal of Medicine,Case 13-2012, illustrating how select key terms from the title of a case history can diagnose a difficult case.
3. Arterial dissection [S]
A PGY-3 neurology resident was called to the emergency department to see a 33 year-old woman with a one day history of pulsatile tinnitus in her right ear. Neurologic examintion was non-focal.
Search strategy: Considering the uniqueness and validity of the patients main complaint, “pulsatile tinnitus”, a single term was chosen for a diagnostic search using NeurologyINDEX.
Comment: The resident can consult NeurologyINDEX on a hand-held device at point-of-care and easily survey a list of 21 diagnostic possibilities for “pulsatile tinnitus” (left panel). Considering the clinical features, seeing arterial dissection on the list can prompt the resident to suggest CT angiography to screen for dissection, the diagnosis in this case. Clicking on the key term in the diagnostic list displays the citation, and clicking on the citation opens citation to display key terms of the citation, and in most cases an abstract (right panel).
4. Neoplastic angioendotheliomatosis [M]
An otherwise healthy 64 year-old-women presented to hospital with new onset grand mal seizure, temperature of 101F, and sedimentation rate of > 100. MR showed 2 small areas of hemorrhage in right frontal lobe surrounded by increased signal on FLAIR. Cerebrospinal fluid (CSF) showed mild lymphocytic pleocytosis. Routine blood and CSF chemistries, cultures, cytology and serology’s including HIV were normal. A transesophageal echocardiogram was normal. Cerebral angiogram was normal and patient was empirically started on 1 gram of solumedrol daily and discharged to a nursing home. Over the next three weeks she improved and a repeat MR showed marked decrease in the frontal lobe lesion. At 4 weeks however, symptoms of headache and confusion returned and repeat head MR showed marked progression of the initially described lesion. A brain biopsy was performed.
Search strategy: Three non-specific valid key terms: intracerebral hemorrhage, pleocytosis and elevated sedimentation rate were selected for the diagnostic search using NeurologicDx.
Comments: This case illustrates how non-specific but valid key terms can be used in a diagnostic search program to suggest a rare diagnosis not considered with traditional diagnostic methods. NeurologicDx generated a checklist of 23 diagnostic possibilities, 2 of which were primary diagnostic considerations (green √ mark). Brain biopsy confirmed the diagnosis of neoplastic angioendotheliomatosis, one of the two strongly suggested diagnoses.
5. Heredetery hemorrhagic telangiectasia [M, S]
A 38 year-old-man with a history of right frontal brain abscess 3 months prior with a good response to IV antibiotic Rx was transferred with new onset of sudden left sided weakness and sensory loss(NIHH=19). Past medical history was significant for two siblings with stroke in their 30’s. MR obtained on admission showed restricted-diffusion in the right middle cerebral artery territory (see Fig. below).
Search strategy: The patient had a prior brain abscess and then developed a stroke months later and has a family history of stroke in several siblings. A search of non-specific but valid terms “abscess, intracerebral” and “cerebrovascular accident”, using NeurolgicDx generated a differential diagnostic list of conditions not previously considered.
Comment 1: Considering the clinical circumstance, neuroimaging and timing of events the majority of conditions in the diagnostic checklist can be eliminated. The list included hereditary hemorrhagic telangietasis (HHT) (center panel) which prompted an investigation of a CT of the chest which showed a pulmonary A-V fistula (see Fig. below). Examination of the mouth revealed telangiectasia of the tongue and lips. (see Fig. below). Although not specific the association of stroke and abscess is so unusual that diseases associated with both conditions readily becomes apparent in a specialty diagnostic search program as shown here. Selecting cross reference from drop-down menu”stars” references for HHT and clicking on reference displays citation with associated key terms (right panel).
Comment 2: When a diagnosis of HHT is considered a “key term profile” of the disease can be viewed and by clicking on the disease in NeurolgicDx and selecting “just this term.” “Hereditery hemorrhagic telangiectasia” appears in the yellow box on the left. Clicking on HHT in the yellow box opens a new window in NeurologyINDEX showing the full key term profile for HHT (see below).
6. Copper deficiency [S, M]
A 41 year-old- woman was admitted to hospital with several months of progressive weakness and sensory changes inher extremities resulting in her inability to walk. She had a history of alcohol abuse, a poor diet and was edentulous requiring daily application of denture adhesive. She had stopped taking her vitamins following her gastric bypass. Neurologic examination showed features of myelopathy, neuropathy and malnutrition(10)(CPC Ann Neurol Jan 2014).
Search strategy 1: In the setting of gastric bypass considering the specialty nature of the diagnostic programs a single term search in NeurologyINDEX using “gastric partitioning” generates a robust diagnostic checklist(see below).
Comment: Scanning the list and considering her history of daily use of denture adhesive the entity of “Copper deficiency” is notable. Clicking on this disease in the list opens the relevant citations.
Search strategy 2: Considering the main clinical features, a multi-term search with NeurolgicDx using the findings of “myelopathy” and “malnutrition” generates a diagnostic list of 12 considerations among which is “copper deficiency”(see below). It’s the cross-refencing of 2 relatively non-specific terms in a specialty program with “smart” algorithms, that can focus the choices not possible in other information retrieval systems.
Comment: Comparatively, this search in other retrieval systems would be non-specific and otherwise unhelpful diagnostically. From the above results clicking on “copper deficiency”, then on the option “just this term” allows the user to link to NeurologyINDEX by clicking “copper deficiency “ in the yellow box, generating a key term profile for this disease entity.
7. Myasthenia gravis [S]
A 67 year-old woman was admitted to hospital with a history of COPD with a chest x-ray and viral studies of respiratory syncitial virus. Her breathing difficulty increased despite high dose steroids and she was transferred to the intensive care unit for traecheal intubation. After several days extubation was performed only to have to be reintubated after 8 hours due to respiratory fatigue. Review of the patients history noted she had eye surgery 1 year prior for “droopy eyelids”.
Search strategy: This case highlights key term selection not from the history, physical or test results but derived by the physician based on clinical events. In this instance the key term that provides the diagnostic clue to the differential checklist was “failure to wean”.
Comment: The term “failure to wean” generates a list of conditions to consider when intubated patients experience difficulty being extubated. Considering the use of high dose steroids and paralytic agents, critical illness myopathy/neuropathy should have been considered in this patient but was not. Search with “failure to wean”generates a short list of 10 or so disease entities. Myasthenia was also a consideration given her prior history of eye surgery for “droopy eyelids”. The checklist shown above provides a focused list of conditions for the physician to survey at point of care that could suggest conditions not considered. Negative serum acetylcholine receptor antibodies favored the diagnosis of critical illness neuromyopathy and the patient improved and weaned from the ventilator over the next two weeks.
8. Whipples disease [M]
A 54-year-old man was referred for neurologic evaluation for decreasing mental functioning. Past medical history was significant for uveitis and a 25 pound weight loss in the past 6 months. Neurologic examination showed mental status changes consistent with dementia with a mini mental status score of 23 and difficulty with upward gaze. MR of the head was normal.
Search strategy: Selecting the terms uveitis, which is relatively uncommon and either weight loss or dementia, both of which are nonspecific but valid, for a diagnostic search with NeurologicDx yield a differential diagnostic list of 15 items for either combination.
Comment: Note a search with uveitis/dementia generates three items on the checklist that have a green √, indicating a direct match. As these conditions are uncommon or rare they may not have been considered by the consulting neurologist. However, selecting 2 terms for a diagnostic search can suggest possibilities beyond what our experience or memory is capable of, and suggest diagnoses and conditions we have previously never considered much less heard of. Whipple’s disease, a rare infectious disease of the T whipplei organism, usually manifests with gastrointestinal symptoms was one such condition suggested (top screen middle panel). Clicking on first citation opens that reference with its associated key terms (top screen right panel). Similarly a search with uveitis/weight loss gives almost identical results that included the diagnosis of Whipple’s disease.
9. Spinal cord ischemia [S]
A 72 year-old-woman presented with a 2 week history of weakness in her lower extremities. An MR of her lumosacral spine showed a lesion on T2-weighted sequence at T9-10 level described as “owl-eye sign”.
Search strategy: Given the presence of an unusual neurologic sign, using NeurologyINDEX for a single term diagnostic search can generate a differential list.
Comment: This example illustrates how an uncommon but relatively unique key term can be used to generate a differential diagnostic list including a variety of infections processes along with spinal cord ischemia and degenerative conditions. In this patients clinical setting spinal cord ischemia is the likely consideration. The feature of “owl-eye sign,” is uncommon however, a search of just a single term with NeurolgyINDEX can prompt the user to consider various possibilities and select the one most appropriate to the clinical situation
10. Wilsons disease [M]
A 25 year-old-man presented with an 8 month history of progressive clumsiness, incoordination and drooling.
Search strategy: Combining two terms for a diagnostic search in NeurologicDx, one non-specific incoordination and one somewhat uncommon drooling a relatively short list of 7 conditions is generated.
Comment: Most conditions on the list can be excluded considering the patients age and clinical context of the case history. However, hepatolenticular degeneration (Wilson disease) remains a viable consideration.The appropriate blood and urine tests were diagnostic for Wilson disease in this patient.
11. Angelman synrome [M]
A 3 year-old child was referred with a history of seizures since one year of age. Examination was non-focal, however the were multiple areas of hypopigmentation of the skin over the extremities and torso.
Search strategy: Selecting two terms, one non-specific, seizure and one relatively unusual hypopigmentation of skin for a diagnostic search in NeurologicDx yield 9 differential diagnostic conditions.
Comment: The nine considerations provide a list of unusual pediatric conditions that may not have otherwise been considered. Among the nine, four (Angelman syndrome, hypomelinosis of Ito, Praeder-Labhart-Willi syndrome and tuberous sclerosus) have a green √ indicating a more direct association of the search terms. Based on the clinical and neuroimagimg results the final diagnosis of the patient described above was Angelman syndrome. Selecting Angelman syndrome from the differential list highlights the key citations for this condition with a gold star (right panel).
12. Lyme disease coulombe [M]
A 67-year-old woman presented with a 3 to 4 week history of low back pain radiating into the anterior aspect of her left thigh with mild left leg weakness with difficulty walking and multiple falls that worsened 2 days prior to admission. She also noted a one month history of headache but no other symptoms. Neurologic examination was noteable for lower motor neuron facial weakness on the left, mild left leg weakness and absent right and left patellar reflex, with an ataxic unsteady gait and resting tremor. MR of lumbosacral spine region showed nerve root enhancement of the cauda equina. MR of the head was normal. Cerebrospinal fluid examinationwas significant for 585 white blood cells/mm3, (90% lymphocytes), protein of 316mg/dL and glucose of 31mg/dL. Cytology and flow cytometry were normal.
Search strategy: The key terms selected for search include the symptom of low back pain, two spinal fluid findings, hypoglycorrachia and pleocytosis and a MR imaging finding of cauda equina enhancement. Despite an initial clinical impression of carcinomatous meningitis, using the above four key terms in NeurologicDx and selecting various 2 or 3 term combinations a differential diagnostic list is generated. The caveat is that doing a 2 term search with relatively non unique terms such as ataxia and tremor, although present in this patient, are not optimum as the differential list will be excessively long. More unique two or 3 term searches from the key terms selected yield a more focused differential. As seen below, searching on 3 of the 4 terms selected: pleocytosis, hypoglycorrachia, and cauda equina,enhancement, generates a 10 item differential, one of which is Lyme disease, the diagnosis in this case.
Comment: Considering the spinal fluid findings and absence of symptoms or other diagnostic tests to suggest malignancy along with the suggested differential list from the diagnostic search, meningoradiculitis due to Lyme disease was considered. Lyme IgG/IgM Index= 8.89.The IgM Western blot in the blood was positive for Lyme disease as was CSF Lyme PCR.The patient was treated with rocephin and her symptoms gradually improved over the ensuing weeks. A Google search using the same key terms did not include Lyme disease. This case emphasizes the success of a diagnostic search is overwhelmingly dependent on the skill of appropriate key term selection.
13. Borrelia miyamotoi NEJM CPC July 2015 [M]
A-28-year old woman admitted to hospital in the summer because of fever, chills, headache, fatigue, and neck stiffness was the subject of a recent NEJM Clinicopathologic Conference(1). She had been well until 5 days before admission. A day prior to admission she traveled to coastal area of Massachusetts she visited weekly. That evening she noted increased fatigue, body aches, and temperature of 38.6 degrees C and was seen at a local emergency department where she was treated with acetaminophen. Over the next 2 days temperature rose to 39.4C. On admission repeat labs showed elevated liver enzymes, and platelet count of 81,000 per cu millimeter. Testing for hepatitis A and B virus suggested protective immunity. Testing was negative for cytomegalovius nucleic acids, HIV, heterophile antibodies, and IgM and IgG antibodies to Borrelia burgdorferi, coxiella burnetti, ehrlichia, and anaplasma. Ceftriaxone and rifampin were administered. Between the 2nd and 5th hospital day her symptoms resolved and a diagnostic test result received.
Search strategy: Considering the symptom profile one can invision a neurologist being asked to see such a patient in consultation. There was no specific neurologic sign/symptom, laboratoy abnormality or imaging result that was unique or diagnostic in this case. Nevertheless, selection of 4 valid key terms, to use in various 3 term diagnostic searches in NeurologicDx can generate a meaningful diagnostic checklist. The terms selected were: headache, fever, thrombocytopenia, and hepatitis.
Comment: Considering NeurologicDx is a neurology specific diagnostic tool the use of three nonspecific key terms from the 4 chosen(2 symptoms, and 2 laboratory values) can generate a diagnostic checklist that suggests possible etiologies that otherwise may not have been considered if relying on experience and memory alone. B. miyamotoi infection, the diagnosis in this case, is the 5th agent of human disease to be transmitted by Ixodes scapularis tick in the northeast United States. Common symptoms are, headache, thrombocytopenia and hepatitis.
1.Cinicopathologic conference,Borrelia miyamotoi infection. Case 24-2015. NEJM 373: 468-475;2015.
14. Neurosyphilis [M]
A 64-year-old-woman presented with progressive cognitive decline over 7 months. On admission, the patient was alert and oriented to person, time , and place, but had hypophonic speech, impaired attention, and severely impaired short-term recall. Remainder of examination was non-focal. An MRI demonstrated bilateral multifocal white matter T2 signal abnormalities involving the mesiotemporal lobes, insular and subinsular regions, and external and extreme capsules. Spinal fluid analysis demonsrated elevated protein (104 mg/dL.), pleocytosis (28 leukocytes/mm3 with 88% lymphocytes), and a glucose level of 95 mg/dL.
Search strategy: Key terms from the case history include 1. mesial temporal lobe, 2. MRI, abnormal, 3.pleocytosis, and 4. temporal lobe lesion, bilateral. Using varying 2 term combinations in NeurologicDx, a limited differential diagnosis is suggested.
Comment: This case was presented as a mystery case in the journal Neurology (1) and responded to by 21 neurology residents only 3 of whom suggested syphilis in the differential diagnosis. In the 2 term NeurologicDx search shown above, using mesial temporal lobe and MRI, abnormal, a 5 item differential diagnosis is suggested that includes neurosyphilis. This “mystery case” serves to highlight our diagnostic limitations (2) while pointing to the usefulness of electronic diagnostic aides in clinical neurology (3, 4). Other 2 term combinations, as terms 1 and 3, and 1 and 4 above, would give similar results.
1. Bhai S, Biffi A, Bakhadirov K, Prasad S. Mystery Case: A 64-year-old-woman with subacute encephalopathy. Neurol 2015; 85: e64-e65.
2. Finelli PF, McCabe AL. Computer generated checklist significantly improves Differential diagnosis in neurologic disease over simple recall. Neurol (abstract). 2014; 82 Suppl (P1.319).
3. WWW.NeurologicDx.com 2.0 open access database 2015.
4. WWW.NeurologyINDEX.com 1.0 open access database 2015.
15. Orinthine transcarbamylase deficiency [M]
A 27 year-old-man found wandering the street and not communicative was brought to a local emergency department(1). Examination showed patient to be stuporous with non-focal examination. Subsequently he developed multifocal myoclonous and was obtunded. Routine blood count and chemistries were normal as was spinal fluid analysis and urine toxicology. CT of head was unremarkable however, MR imaging showed restricted-diffusion involving the frontal, temporal and occipital lobes and insular cortex cortex (Figure). The diffusion-weighted image is shown in panel (A) and the apparent diffusion coefficient in (B).
Search strategy: Staying with the strategy of unique and valid as key term criteria terms as myoclonous, MRI,diffusion-weighted, cerebral cortex or cortical ribbon can be selected then using NeurologicDx a 2 or 3 term search can be done.
Comment: The diagnosis in this case turned out to be a rare inborn error of metabolism caused by ornithine transcarbamylase deficiency. By using NeurologicDx and searching on MRI,diffusion and cerebral cortex a 36 item checklist differential diagnosis is generated. Scanning the list most entries can easily be eliminated knowing the clinical history. Two conditions noted in the list were ammonia and hyperammonemic encephalopathy which prompted checking the ammonia level that was found to be markedly abnormal. Once an elevated ammonia was discovered and causally linked, the focus can shift to determine the etiology of the elevated ammonia in an otherwise healthy 27 year-old-man(2, 3).
1. Wong JM, et al. A 27 – year-old man with rapidly progressive coma. Neurol 2015; 85: e74-e78.
2. Walker V, Ammonia toxicity and its prevention in inherited defects of the urea cycle. Diabetes Obes Metab 2009; 11: 823-835.
3. Takamashi J, Bardovich AJ, Cheng SF, Kostiner D, Baker JC, Packman S. Brain MR imaging in acute hyperammonemic encephalopathy arising from late-onset ornithine transcarbamylase deficiency. Am J Nuroradiol 2003; 24; 390-393.
16. Molybdenum cofactor defficiency [S]
Case 16. A Grand Rounds presentation in August 2015 was that of a 4 day old infant brought to our emergency department after parents witnessed a generalized tonic-clonic seizure. The pregnancy and delivery were uneventful. Patient had a complete blood count and rotine chemistry profile that was normal other than for a low serum uric acid level. Examination was non-focal. Additoional history from mother describes infant as irritable with poor feeding and a poor suck. CT and MR were unremarkable other than cavitary areas in frontal parenchyma on T1-weighted sequence. A skeletal servey showed a fracture of the right clavicle.
Search strategy: Using NeurologyINDEX a single term search on either poor suck, poor feeding or uric acid, low was performed.
Comment: A single term search can be effective considering the uniqueness of the term. In the above case where the diagnosis was illusive and ultimately determined to be due to molybdenum cofactor deficiency a search with either poor suck, poor feeding or uric acic, low would have generated a short list including molybdenum deficiency. Just seeing molybdenum in the differential list could have avoided delay in diagnosis(1).
1. Reiss J, Johnson JL. Mutation in the molybdenum……. . Human Mutat 2003; 21: 569-576.
17. Diabetes dialysis basal ganglia syndrome [M]
A 47 year-old- Hispanic female with insulin-dependant diabetes on dialysis developed headache and gait difficulty over the preceeding 2 weeks. Neurologic examination was unremarkable other than for mild parkinsonian features. CT (left)and MR- FLAIR (right) imaging of the head showed bilateral basal ganglia lesions.
Search strategy: The neurologic examination was non-focal and despite the neuroimaging findings diagnosis was uncertain. Selecting 4 rather nonspecific but valid terms: diabetes, dialysis, gait difficulty, and parkinsonism syndrome a diagnostic search was undertaken. Using variable 2 term combinations and scanning the differential list generated, a condition as seen in this patient was noted among the results.
Comment: This case illustrates how combining even common key terms can generate a focused differential list helpful in the diagnosis of a rare condition seen primarily in the Asian population (1).
1. Finelli PF and Singh JU. A syndrome of bilateral symmetricl basal ganglia lesions in diabetic dialysis patients. Am J Kidney Dis 2014; 63: 286-288.
18. Rabies [M]
A 63-year-old man was well until a day prior when he developed paresthesias and difficulty drinking liquids. His examination was non-focal and CT and MR of the head was unremarkable. Routine laboratory test were normal however, cerebrobspinal fluid examination showed 39 cells/cumm, predominatly lymphocytes. He then developed a low grade temperature with a fluctuating blood pressure and pulse. His condition progressively worsened over the next several weeks and he expired on the 30th hospital day.
Search strategy: In this case 2 rather non-specific but valid key terms, as paresthesias and dysphagia were used in the search process.
Comment: This case illustrates how 2 rather non-specific terms can yield a meaningful and focused checklist. The differentil list consists of 17 considerations 2 of which are marked with a green check (√) to indicate a direct association. One of the choices was Rabies, the diagnosis in this case (1). Selecting reference displays citation and associated key terms.
1. Clinicopathologic conference, Rabies encephalitis, Case record 1-2013. New Engl J Med. 2013; 368: 172-180.
19. Cerebral amyloid angiopathy [S]
A 63-year-old woman with a negative past medical history, noticed drooping of the left side of her face, slurred speech and left arm weakness and numbness, lasting 1 hour. A head CT and MR was performed and showed a convexity subarachnoid hemorrhage.
Search strategy: Searching on a single term that is both valid and unique can generate a focused differential diagnostic list. In this patient convexity subarachnoid hemorrhage was selected as the key term for the search.
Comment: A search on convexity subarachnoid hemorrhage generated a list of 22 considerations. Knowing the clinical circumstance of the case, the majority of conditions can be excluded. Included among the few remaining considerations is cerebral amyloid angiopathy, a condition that otherwise may not have been considered among the diagnostic possibilities. This search could have been done with either NeurologicDx or NeurologyINDEX, where the former gives a differential diagnosis of the key term, and the later a broader list of associated features in addition to the differential diagnosis..
20. Acute intermittent porphyria [M]
A 23-year-old woman from Peru presented to our emergency department with a several day history of nausea and vomiting, abdominal pain and difficulty walking. Her past history was negative other than a history of seizure several weeks prior, while in Peru. Examination showed diffuse 3/5 weakness including the neck flexor muscles. Laboratory values included a normal complete blood count and blood urea nitrogen. Serum sodium was 113mmol/L and lipase was 1137u/L.
Search strategy: In this case two abnormal laboratory values i.e. low sodium (hyponatremia) and elevated lipase were selected as key terms for the search.
Comment: Only 2 items appear on the differential list, one of which was acute intermittent porphyria, the diagnosis in this case. It’s important to keep in mind the database is specialty specific to neurology, thus all results in the list are neurologically related entities.