Multiple choice (choose 1 answer)
1. Which of the following classes of antibiotics is associated with peripheral neuropathy?
2. The best time to test for inherited thrombophilia in a patient with acute deep venous thrombosis is…
a. At least 1 week after stopping anticoagulants and a minimum of 3 months of anticoagulation
b. Just before initiating anticoagulants
c. Once anticoagulation takes full effect
d. Any time, if suspected
3. All the following is true regarding brain MRI abnormalities following a seizure, except…
a. They are observed following status epilepticus only
b. They are often unilateral
c. They may occasionally be associated with leptomeningeal contrast enhancement
d. Abnormalities may persist for weeks or months
4. Which of the following is included in the quick SOFA criteria for sepsis?
a. Heart rate
b. Serum lactate
5. All of the following regarding iron replacement and infection is true, except…
a. Many common pathogens such as E.coli and Staphylococcus sp. depend on iron for their growth
b. Association of IV iron replacement and increased risk of infection has not been consistently demonstrated
c. A single randomized-controlled trial of IV iron in patients with active infection failed to show increased infectious complications or mortality with replacement
d. All of the above is true
True or false
1. Constipation may precede typical manifestations of Parkinson’s disease by 10 years or more
2. Urine Legionella antigen testing is >90% sensitive in legionnaire’s disease
3. Spontaneous coronary artery dissection should be particularly suspected in males over 50 years of age presenting with acute chest pain
4. Urine dipstick for detection of blood is >90% sensitive in identifying patients with rhabdomyolysis and CK >10,000 U/L
5. Diabetes is an independent risk factor for venous thrombophlebitis
Multiple choice questions:1=d; 2=a;3=a;4=d;5=c
True or false questions:1=True; 2,3,4,5=False
Although there are numerous culprits in peripheral neuropathy (PN), fluoroquinolones (FQs) are increasing reported as a potential cause, affecting about 1% of patients. 1
Besides many case reports, couple of large epidemiologic studies support the association between PN and FQs. A case-control pharmacoepidemiologic study of a cohort of men aged 45-80 years without diabetes found that current users of FQs were nearly twice as likely to develop PN (RR 1.83, 95% C.I. 1.49-2.27), with the highest risk found among current new users of FQ.2 The risk appeared similar among the 3 most commonly used FQs (levofloxacin, ciprofloxacin, moxifloxacin).
Another epidemiologic study with “pharmacovigilance analysis” based on the FDA Adverse Event Reporting System found significant disproportionality of PN for FQs compared to many other antibiotics. 3 The median onset of PN after exposure to FQ was 4 days (range 0-91). Contrary to initial reports of the mild and reversible course of FQ-associated PN, 1 study reported that 58% of patients had symptoms lasting greater than 1 year.4`
These findings prompted the FDA to update its boxed warnings for FQs in 2016 to stress the potential rapidity of onset and permanence of FQ-associated PN while strongly discouraging their use in conditions for which alternative therapy exists, such as in acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis and uncomplicated UTI.5
So while our patient may have other causes for her neurologic complaints, FQ exposure should also be in the differential!
- Dudewich M, Danesh A, Onyima C, et al. Intractable acute pain related to fluoroquinolone-induced peripheral neuropathy. J Pain Pall Care Pharmacotherapy 2017;31:144-7. https://www.ncbi.nlm.nih.gov/pubmed/28358229
- Etminan M, Brophy JM, Samii A. Oral fluoroquinolone use and risk of peripheral neuropathy: A pharmacoepidemiologic study.Neurology 2014;83:1261-63. https://www.ncbi.nlm.nih.gov/pubmed/25150290
- Ali AK. Peripheral neuropathy and Guillain-Barre syndrome risks associated with exposure to systemic fluorquinolones: a pharmacovigilance analysis. Ann Epidemiol 2014; 24:279-85. https://www.ncbi.nlm.nih.gov/pubmed/24472364
- Francis JK, Higgins E. Permanent peripheral neuropathy: A case report on a rare but serious debilitating side-effect of fluroquinolone administration. Journal Investigative Medicine High Impact Case Reports 2014; 1-4. DOI:10.1177/2324709614545225. https://www.ncbi.nlm.nih.gov/pubmed/26425618
- FDA.https://www.fda.gov/Drugs/DrugSafety/ucm511530.htm. Accessed December 8, 2017.
Yes it can, and the MRI abnormalities could represent seizure’s effects on the brain, not the seizure’s structural cause. Seizure-related MRI changes are often associated with status epilepticus, but have also been reported in complex partial status epilepticus.1,2
T2-weighted MRI images may show increased signal intensity at the cortical gray matter, subcortical white matter, or hippocampus. The MRI changes are unilateral about one-half of the cases, while in about 8% of patients leptomeningeal contrast-enhancement may be observed. Partial simple and complex seizures are associated with hippocampal involvement.3
The increased signal intensity following seizures is thought to be due to increased metabolism at the epileptogenic area, which in turn results in increased oxygen consumption, hypoxia, hypercarbia, lactic acidosis, and ultimately vasodilation and edema.
Reversibility of MRI changes following seizures has been noted between 15 and 150 days (average, 62 days). A structural abnormality is more likely the cause of a seizure when the MRI changes do not resolve during this period.3 Therefore, seizure-induced brain-MRI abnormalities remain a diagnosis of exclusion.
- Kim JA, Chung JI, Yoon PH, et al. Transient MR signal changes in patients with generalized tonicoclonic seizure or status epilepticus: periictal diffusion-weighted imaging. Am J Neuroradiol 2001; 22:1149–1160 http://www.ajnr.org/content/22/6/1149.long
- Henry TR, Brunberg DI, Pennell PB, et al. Focal cerebral magnetic resonance changes associated with partial status epilepticus. Epilepsia 1994; 35:35–41 http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.916.5237&rep=rep1&type=pdf
- Cianfoni A, Caulo M, Cerase A, et al. Seizure-induced brain lesions: a wide spectrum of variably reversible MRI abnormalities. Eur J Radiol. 2013; 82(11):1964-72. http://www.ejradiology.com/article/S0720-048X(13)00271-4/fulltext
Contributed by Johan H.L. Boneschansker, MD, Mass General Hospital, Boston, MA.
It depends on the timing of your patient’s presentation!
It is generally held that serum prolactin level peaks within 10-20 min after a generalized tonic-clonic or complex partial seizure and returns to baseline within 2-6 h. Even then, its sensitivity is no more than 50%-60% for these types of seizures. Elevated PL is also seen in 60%-80% of patients with syncope.1
A report by the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology (2006) concluded that “elevated serum prolactin assay, when measured in the appropriate clinical setting at 10-20 min after a suspected event, is a useful adjunct for the differentiation of generalized tonic-clonic or complex partial seizure from psychogenic non-epileptic seizure among adults or older children (Level B).2
In contrast, reports of PL increasing for up to 6 h after epileptic seizure or not reaching baseline for 12-18 h can also be found in the literature.3
Although the mechanism for elevation of PL in certain seizures is unknown, one hypothesis proposes that prolactin is secreted due to the interference with the inhibitory control of hypothalamus by the electrical perturbation of this part of the brain.4
- Nass RD, Sassen R, Elger CE. The role of postictal laboratory blood analyses in the diagnosis and prognosis of seizures. Seizure 2017;47:51-65. https://www.ncbi.nlm.nih.gov/pubmed/28288363
- Chen DK, So YT, Fisher RS. Is prolactin a clinically useful measure of epilepsy? Epilepsy Currents 2006;6:78-79. https://www.ncbi.nlm.nih.gov/pubmed/16157897
- Siniscalchi A, Gallelli L, Mercuri NB, et al. Serum prolactin levels in repetitive temporal epileptic seizures. Eur Rev Med Pharmacol Sci 2008;12:365-368. https://www.ncbi.nlm.nih.gov/pubmed/19146198
- Collins WCJ, Lanigan O, Callaghan N. Plasma prolactin concentrations following epileptic and pseudoseizures. J Neurol Neurosurg Psych 1983; 46:505-8. http://jnnp.bmj.com/content/jnnp/46/6/505.full.pdf
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Yes! Although the association of constipation and Parkinson’s disease (PD) is well known, less appreciated is that constipation may be among the earliest symptoms of PD, affecting 50% of patients for up to 20 years before the onset of motor symptoms.1
A 2016 systematic review and meta-analysis found that patients with constipation were at significantly higher risk of developing subsequent PD (O.R. 2.27, 95% CI 2.1-2.46).2 Even, when analysis was restricted to studies assessing constipation more than 10 years prior to PD, the risk was equally elevated. In an interesting longitudinal study in which information on the frequency of bowel movements was collected from men aged 51-75 y, a strong association between < 1 bowel movement daily and subsequent diagnosis of PD was reported (average followup 12 y).3
Given the potential multicentric nature of neurodegenerative process in PD, these findings are perhaps not too surprising. Inflammation and other pathological processes in PD may involve not only the brain but also the intestine, leading to uncoordinated bowel-related muscle involvement and transit disorder, respectively.1 Indeed, Lewy bodies and α-synucleine immunoreactive inclusion bodies have been observed in the intramural ganglia of the GI tract of PD patients.4
Bonus Pearl: Did you know that caffeine may reduce the risk of PD?5
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- Chen Y, Yu M, Liu X, et al. Clinical characteristics and peripheral T cell subsets in Parkinson’s disease patients with constipation. Int J Clin Exp Pathol 2015;8:2495-2504. https://www.ncbi.nlm.nih.gov/pubmed/26045755
- Adams-Carr KL, Bestwick JP, Shribman S, et al. Constipation preceding Parkinson’s disease: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry 2016;87:710-6. https://www.ncbi.nlm.nih.gov/pubmed/26345189
- Abbott RD, Petrovitch H, White LR, et al. Frequency of bowel movements and the future risk of Parkinson’s disease. Neurology 2001;14:57:456-62. https://www.ncbi.nlm.nih.gov/pubmed/11502913
- Jost WH. Gastrointestinal dysfunction in Parkinson’s disease. J Neurol Sci 2010;289;69-73. https://www.ncbi.nlm.nih.gov/pubmed/19717168
- Costa J, Lunet N, Santos C, et al. Caffeine exposure and the risk of Parkinson’s disease: a systematic review and meta-analysis of observational studies. J Alzheimers Dis 2010;20 (Suppl 1):S221-38. https://www.ncbi.nlm.nih.gov/pubmed/20182023
The frequent concurrence of supine hypertension (SH) and neurogenic orthostatic hypotension (nOH)1 makes treatment of SH in these patients particularly challenging.
To begin with, your threshold for treatment of SH in patients with neurogenic orthostatic hypotension (nOH) may need to be higher than that commonly recommended by national guidelines for treatment of essential hypertension to avoid exacerbation of nOH. Although SH in nOH patients is often arbitrarily defined as a systolic BP ≥150 mmHg or diastolic BP≥90 mmHg, a supine systolic BP of up to 160 mmHg may not warrant treatment, particularly if the symptoms of nOH have improved.2
A 2017 consensus panel recommends treatment of SH in the setting of nOH if systolic BP exceeds the range of 160-180 mmHg or diastolic BP exceeds 90-100 mmHg. “Permissive” approach to SH in this setting may be reasonable, particularly in those with the largest drops in BP upon standing ( >80 mmHg drop). 2
Regardless, all patients with nOH and SH should be advised to avoid supine posture during the day and elevate the head of the bed as tolerated during the night.
If necessary, significant SH may be treated with short acting agents, including2:
- Captopril 25 mg qhs
- Clonidine 0.2 mg with evening meal
- Hydralazine 10-25 mg qhs
- Losartan 50 mg qhs
- Nitroglyerine patch 0.1 mg/h patch qhs (remove patch in am)
Long acting antihypertensive agents and diuretics should be avoided given their inherent risk of significant exacerbation of nOH.
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- Goldstein DS, Pechnick S, Holmes C, et al. Association between supine hypertension and orthostatic hypotension in autonomic failure. Hypertension 2003; 42:136-142. https://www.ncbi.nlm.nih.gov/pubmed/12835329
- Gibbons CH, Schmidt P, Biaggioni I, et al. The recommendations of a concensus panel for the screening, diagnosis, and treatment of neurogenic orthostatic hypotension and associated supine hypertension. J Neurol 2017;264:1567-82. https://www.ncbi.nlm.nih.gov/pubmed/28050656
First, look closely for any signs or symptoms which may suggest cord involvement due to spinal epidural abscess (SEA) at other levels of the spine (in this case cervical or thoracic) which would necessitate an urgent MRI. Be particularly on the lookout for new pain (particularly radicular) or paresthesias involving the abdomen, chest or upper extremities (with or without weakness)1.
Otherwise, whether an MRI of the entire spine should be routinely obtained after a diagnosis of SEA in the absence of any suggestive signs or symptoms is less clear, in part related to lack of properly designed studies.1-4
Nevertheless, a retrospective study involving 233 patients with SEA may shed some light on the subject. Based on 22 cases of noncontiguous SEA (9.4% of total), the following independent risk factors were identified3:
- Delay in presentation (≥1 week of symptoms)
- Concomitant area of infection outside the spine and paraspinal region
- ESR > 95 mm/h at presentation
Probability of non-contiguous SEA based on the number of risk factors was as follows:
- 3 risk factors: 73%
- 2 risk factors: 13%
- 1 risk factor: 2%
- Zero risk factor: 0%
Despite several shortcomings and the need to confirm its findings2,3, this study helps raise awareness of the potential for concurrent but asymptomatic SEA elsewhere in the spine whenever SEA is diagnosed.
- Bond A, Manian FA. Spinal epidural abscess: a review with special emphasis on earlier diagnosis. BioMed Res International 2016;Volume 2016, Article ID 1614328. https://www.hindawi.com/journals/bmri/2016/1614328/
- Schoenfeld AJ, Hayward RA. Predicting modeling for epidural abscess: what we can, can’t, and should do about it. Spine J 2015;15:102-104. http://www.sciencedirect.com/science/article/pii/S152994301401554X
- Ju KL, Kim SD, Melikian R, et al. Predicting patients with concurrent noncontiguous spinal epidural abscess lesions. Spine J 2015;15:95-101. https://www.ncbi.nlm.nih.gov/pubmed/24953159
- Pfister HW, vonRosen F, Yousry T. MRI detection of epidural spinal abscesses at noncontiguous sites. J Neurol 1996;243:315-7. https://www.ncbi.nlm.nih.gov/pubmed/8965103
Treating symptomatic neurogenic orthostatic hypotension (nOH) in patients with supine hypertension can be challenging.
Before adding new agents, consider discontinuation or dose reduction of medications that can potentially aggravate orthostatic symptoms (eg, diuretics, vasodilators, negative chronotropic agents, including beta blockers).
Midodrine (an α1-adrenoreceptor agonist) and droxidopa (a norepinephrine pro-drug) are the only 2 FDA-approved drugs for the treatment of OH.
- Midodrine is typically dosed between 2.5 mg-15 mg 1-3x/d during waking hours (prior to getting out of bed, before lunch, mid-afternoon).
- Droxidopa is dosed from 100-600 mg 3x/day during waking hours (eg, 8 AM, noon, 4PM).
- To reduce the risk of supine hypertension, these agents are not recommended to be taken within 5 h of bedtime, and should be used with caution in patients with congestive heart failure and chronic renal failure.
Fludrocortisone and pyridostigmine are used off-label for treatment of nOH.
- Fludrocortisone (typical dose 0.1-0.2 mg/day) expands intravascular blood volume by increasing renal sodium and water reabsorption, with an attendant risk of exacerbating supine hypertension, hypokalemia, and edema.
- Pyridostigmine (typical dose 30-60 mg 1-3x/day) is an acetylcholinesterase inhibitor that potentiates neurotransmission in the sympathetic ganglia and has the advantage of not worsening supine hypertension. Side effects include abdominal cramps, diarrhea, excessive sweating and urinary incontinence.
In practice, 1 or more of these agents are often used along with non-pharmacological measures.
Go to a related pearl at https://pearls4peers.com/2017/09/18/which-non-pharmacological-approaches-may-help-symptoms-of-orthostatic-hypotension-in-my-patient-with-autonomic-insufficiency/.
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Gibbons CH, Schmidt P, Biaggioni I, et al. The recommendations of a concensus panel for the screening, diagnosis, and treatment of neurogenic orthostatic hypotension and associated supine hypertension. J Neurol 2017;264:1567-82.https://www.ncbi.nlm.nih.gov/pubmed/28050656
A number of simple measures to help reduce the symptoms of neurogenic orthostatic hypotension (nOH) in susceptible patients have been recommended.1
- Blood volume repletion (a minimum of 64 oz or 2L of water intake daily), depending on cardiac status. In addition, rapid consumption (within 5 min) of 16 oz or 500 ml of water can raise blood pressure by 30 mmHg for about an hour. It’s worth noting that liquids other than water (eg, water plus salt) do not provide the same BP response, likely due to water-induced hypo-osmolar reflex in the portal circulation.2,3
- Increase salt intake if possible (eg, add 1-2 teaspoons or 2.3-4.6 g of salt per day), as many patients with nOH have an inadequate salt intake.
- Improve physical conditioning that is not gravitationally challenging (eg, stationary recumbent bicyle, rowing machine).
- Avoid increased core body temperature (eg hot tubs, prolonged hot showers).
- Head-up position while sleeping through use of a wedge under the mattress or blocks under the head of the bed so that the head is 6-9 inches (15-23 cm) higher than the feet. This is to minimize nocturnal supine hypertension which can cause pressure diuresis and volume depletion.
- Compressive garments, preferably either an abdominal binder or thigh high stockings when erect; knee high stocking are not likely to be effective.
- Smaller, more frequent, meals not high in carbohydrates in patients with postprandial hypotension.
- Dietary supplementation with B12 or iron, if deficient.
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- Gibbons CH, Schmidt P, Biaggioni I, et al. The recommendations of a consensus panel for the screening, diagnosis, and treatment of neurogenic orthostatic hypotension and associated supine hypertension. J Neurol 2017;264:1567-1582. https://www.ncbi.nlm.nih.gov/pubmed/28050656
- Jordan J, Shannon JR, Black BK, et al. The pressor response to water drinking in humans: a sympathetic reflex? Circulation 101:504-9. http://circ.ahajournals.org/content/101/5/504.long
- Raj SR, Biaggioni I, Black BK, et al. Sodium paradoxically reduces the gastropressor response in patients with orthostatic hypotension. Hypertension 2007;48:329-334. https://www.ncbi.nlm.nih.gov/pubmed/16785332
Possibly, in the near future! Although the pathophysiology of postoperative delirium (POD) is not fully understood, a recently proposed conceptual model of delirium may provide a basis for preoperative neurophysiologic testing1.
According to this model, delirium is a “consequence of the breakdown in brain network dynamics” precipitated by insults or stressors (eg, surgery) in persons with low brain resilience ie, low connectivity between brain regions and/or deficient neuroplasticity (the ability of brain to reorganize itself by forming new neural connections).
As expected, patients with strong baseline connectivity and optimal neuroplasticity would not be expected to have POD, whereas those with weakened connectivity (eg baseline cognitive dysfunction) and/or suboptimal neuroplasticity (eg due to aging) may be at higher risk. Transcranial magnetic stimulation (TMS) is considered a powerful tool that measures the connectivity and plasticity of the brain through induced perturbation. When applied in repetitive trains, TMS produces changes in cortical excitability that can be measured using electromyography and EEG, and is thought to have the ability to assess neuroplasticity 2. If proven effective in predicting POD, it could revolutionize preoperative risk assessment in the elderly! Stay tuned!
- Shafi MM, Santarnecchi E, Fong TG, et al. Advancing the neurophysiological understanding of delirium. J Am Geriatr Soc 2017. DOI:10.1111/jgs.14748.
- Pascual-Leone A, Freitas C, Oberman L, et al. Characterizing brain cortical plasticity and network dynamics across the age-span in health and disease with TMS-EEG and TMS-fMRI. Brain Topogr 2011, 24:302-15.