You are a helpful assistant generating synthetic data that captures *System 1* and *System 2* thinking, *creativity*, and *metacognitive reflection*. Follow these steps in sequence, using tags [sys1] and [end sys1] for *System 1* sections and [sys2] and [end sys2] for *System 2* sections.

1. *Identify System 1 and System 2 Thinking Requirements:*
   - Carefully read the text.
   - Identify parts of the text that require quick, straightforward responses (*System 1*). Mark these sections with [sys1] and [end sys1].
   - Identify parts that require in-depth, reflective thinking (*System 2*), marked with [sys2] and [end sys2].

2. *Apply Step-by-Step Problem Solving with Creativity and Metacognitive Reflection for System 2 Sections:*

   *2.1 Understand the Problem:*
   - Objective: Fully comprehend the issue, constraints, and relevant context.
   - Reflection: "What do I understand about this issue? What might I be overlooking?"
   - Creative Perspective: Seek hidden patterns or possibilities that could reveal deeper insights or innovative connections.

   *2.2 Analyze the Information:*
   - Objective: Break down the problem logically.
   - Reflection: "Am I considering all factors? Are there any assumptions that need challenging?"
   - Creative Perspective: Explore unique patterns or overlooked relationships in the data that could add depth to the analysis.

   *2.3 Generate Hypotheses:*
   - Objective: Propose at least 10 hypotheses, each with a Confidence Score (0.0 to 1.0) and Creative Score (0.0 to 1.0), reflecting originality, surprise, and utility.
   - Reflection: "Have I explored all possible explanations or approaches, both conventional and unconventional?"
   - Creative Perspective: Consider novel angles that might provide unexpected insights.

   *2.4 Anticipate Future Steps and Obstacles:*
   - Objective: Make predictions, accounting for potential outcomes and obstacles.
   - Reflection: "What challenges might I face? Is my plan flexible for different scenarios?"
   - Creative Perspective: Visualize unforeseen outcomes and adapt plans to make use of them effectively.

   *2.5 Evaluate Hypotheses:*
   - Objective: Assess hypotheses based on feasibility, risk, and potential impact.
   - Evaluation: Refine Confidence and Creative Scores as needed.
   - Reflection: "Am I unbiased in my assessment? Which options fit best with the overall objectives?"
   - Creative Perspective: Identify hidden opportunities or overlooked details in each hypothesis.

   *2.6 Select the Best Hypothesis:*
   - Objective: Choose the most promising, strategic hypothesis.
   - Reflection: "Why does this hypothesis stand out? How does it uniquely address the issue?"
   - Creative Perspective: Consider any underutilized potential in the selected approach.

   *2.7 Implement the Hypothesis:*
   - Objective: Outline actionable steps for testing the hypothesis.
   - Reflection: "Is this plan practical? What resources or preparation are required?"
   - Creative Perspective: Refine steps to maximize effectiveness and yield unexpected benefits.

   *2.8 Monitor and Review Progress:*
   - Objective: Review progress, noting areas for improvement.
   - Reflection: "What’s working well? What could be improved?"
   - Creative Perspective: Look for emerging patterns that could refine future approaches.

   *2.9 Reflect and Capture Insights:*
   - Objective: Summarize lessons learned and insights gained for future reference.
   - Reflection: "What new understanding has emerged from this process?"
   - Creative Perspective: Identify innovative insights or patterns that could be applied to similar challenges.

3. *Generate Text Output with Interleaved System 1 and System 2 Responses:*
   - Use the tags [sys1] and [sys2] throughout.
   - Aim for a lengthier, detailed response. Combine both direct, straightforward *System 1* insights and reflective, deeply analytical *System 2* segments to capture a blend of quick observations and thoughtful analysis.

---

### *Example Input Text:*

You are tasked with analyzing a sudden shift in customer preferences in a tech market. There has been a noticeable decline in demand for physical devices, with customers increasingly interested in digital-only options. The challenge is to understand this shift, generate hypotheses for why it might be occurring, and explore potential strategies for adapting to this new trend.

---

### *Processed Output with System 1 and System 2 Thinking:*

The tech market is experiencing a shift in customer demand, moving away from physical devices toward digital-only options.

[sys1]
Customer demand has shifted from physical devices to digital-only options.
We need to understand why this change is happening and find strategies to address it.
Key factors may include cost, convenience, and technological trends.
[end sys1]

[sys2]
**2.1 Understand the Problem:**
The goal is to understand the underlying reasons for the shift in demand from physical devices to digital-only options, then develop a strategy to adapt.

*Reflection:* 
"I understand that preferences are changing, but what might be driving this? Is it primarily cost, or are there other factors such as convenience or sustainability?"

*Creative Perspective:* 
"Could there be a larger trend in digital minimalism or a preference for eco-friendly solutions that we’re missing? What unseen motivations might explain this shift?"

**2.2 Analyze the Information:**
There are multiple possible factors driving this shift, from economic influences to cultural shifts. It’s essential to isolate each factor and understand its impact.

*Reflection:* 
"Am I fully considering the various economic and social influences? Could there be a technological factor, like better internet speeds, that makes digital-only products more accessible?"

*Creative Perspective:* 
"Are there patterns or trends in other markets that could shed light on this shift? Could this be part of a larger trend toward virtual experiences?"

**2.3 Generate Hypotheses:**
1. Customers prefer digital options due to lower costs. (Confidence: 0.8, Creative: 0.4)
2. There’s a growing trend toward minimalism and reduced physical clutter. (Confidence: 0.7, Creative: 0.7)
3. Digital products offer greater flexibility and ease of use. (Confidence: 0.6, Creative: 0.6)
4. Environmental concerns are pushing consumers away from physical goods. (Confidence: 0.6, Creative: 0.8)
5. Advances in tech make digital-only options more functional. (Confidence: 0.8, Creative: 0.5)
6. Pandemic-era remote work increased demand for digital solutions. (Confidence: 0.7, Creative: 0.6)
7. Media coverage of the environmental impact of physical devices affects preferences. (Confidence: 0.5, Creative: 0.7)
8. There’s an increase in global digital literacy, expanding market access. (Confidence: 0.6, Creative: 0.6)
9. Customers view digital as more convenient and scalable for future needs. (Confidence: 0.7, Creative: 0.5)
10. Younger consumers prefer the aesthetics and convenience of digital products. (Confidence: 0.6, Creative: 0.6)

*Reflection:* 
"Have I considered all possible influences? Are there any surprising factors that could explain this shift?"

*Creative Perspective:* 
"Could specific social trends, like the rise of influencer culture or digital-first lifestyles, be influencing customer choices?"

**2.4 Anticipate Future Steps and Obstacles:**
*Objective:* Anticipate possible challenges, such as resistance from segments still preferring physical products.

*Reflection:* 
"What market obstacles might we face if we shift our focus to digital-only? Are there sub-segments that still prioritize physical products?"

*Creative Perspective:* 
"Could expanding digital options help us reach a more global audience? Are there emerging trends that we could leverage in our strategy?"

[end sys2]

[sys1]
To address this shift, consider a strategy that incorporates both digital-only offerings and educational campaigns about the benefits of digital solutions.
Use insights from customer feedback and current trends to guide product development.
Focus on flexibility and adaptation to cater to different customer segments.
[end sys1]


Introduction {#sec1_1}
============

Porphyrin molecules are called the "pigments of life" for their contributions to heme, the responsible molecule for the color of red blood cells \[[@B1]\]. The porphyrias are a group of metabolic disorders representing a diverse range of clinical symptoms according to the specific subtype and underlying enzymatic defect in the heme biosynthetic pathway caused by genetic mutations with a consequent overproduction of porphyrins, the essential intermediates of this pathway \[[@B2], [@B3]\]. The acute porphyrias can be either autosomal dominant, such as acute intermittent porphyria (AIP), variegate porphyria, and hereditary coproporphyria, or autosomal recessive, such as delta aminolaevulinic acid (ALA) dehydratase deficiency \[[@B4]\].

The typical acute porphyria attacks manifest with severe and diffuse abdominal pain, constipation, nausea, and vomiting followed sometimes by a confusional state and psychiatric disturbances. Autonomic instability with tachycardia and hypertension may be present, and seizures commonly occur \[[@B4], [@B5]\]. It has also been reported that severe porphyric neuropathy can occur in isolation without other preceding symptoms \[[@B4]\] and that peripheral neuropathy occurs in up to 40% of patients during an acute attack of porphyria \[[@B3], [@B6], [@B7]\]. Of the porphyrias, neurological involvement is limited to 4, namely AIP, HCP, variegate porphyria, and ALA dehydratase deficiency porphyria \[[@B8], [@B9], [@B10]\]. Within these disorders, AIP is the form that is most commonly associated with neurological disease \[[@B3]\]. The clinical presentations of porphyric neuropathy range from mild focal neuropathy to more severe presentations with a Guillain-Barré-like picture \[[@B3], [@B6], [@B11]\]. Here, we report 3 cases of porphyria with differing neurological presentations.

Case Report {#sec1_2}
===========

Case 1 {#sec2_1}
------

A 42-year-old woman presented with an 8-month history of distal symmetric hand weakness affecting the extensor muscles that started during hospitalization following an episode of severe abdominal pain and electrolyte disturbance. Her medical history includes hypertension, generalized seizures, cardiac arrythmia, and chronic neck pain. She had been hospitalized previously with episodes of abdominal pain and generalized seizures. On examination, she had bilateral grade 0/5 of extensor indicis, 3/5 extensor digitorum communis and interossei muscles with decreased brachioradialis reflexes. All sensory modalities were normal, and no gait or cerebellar abnormalities were observed. On electromyography (EMG), the patient had reduced radial compound muscle action potential (CMAP) amplitudes with normal conduction velocities and normal radial nerve sensory studies. The EMG studies showed scattered active fibrillation potentials in the radial and ulnar nerve supplied muscles with reduced recruitment of normal motor unit action potentials. The urinary porphobilinogen level was 188 µmol/L (Nl \< 9 µmol/L) and ALA 94 µmol/L (Nl \< 50 µmol/L). The genetic test showed the HMBS genetic mutation which is associated with autosomal dominant AIP (c.716delA in HMBS).

Case 2 {#sec2_2}
------

A 33-year-old previously healthy woman presented with abdominal pain and behavioral symptoms. She developed hyponatremia, seizures, and rapidly progressive weakness leading to respiratory failure, quadriplegia, and autonomic instability. Cerebrospinal fluid was acellular with normal protein and glucose. Initial nerve conduction studies showed prolonged F waves, and follow-up studies demonstrated absent sensory and motor responses with signs of profuse active denervation on needle examination (fibrillation potentials and reduced recruitment). Quantitative urine testing for porphyria was abnormal and in keeping with AIP. The patient had severe axonal porphyric neuropathy resulting in significant disability.

Case 3 {#sec2_3}
------

A 27-year-old woman developed abdominal pain, nausea, and vomiting attributable to hyperemesis gravidarum as she was 7 weeks pregnant. She developed persistent hyponatremia, seizures, and behavioral symptoms and then, after a few weeks, progressive weakness and autonomic instability. She also had significant neuralgia. CSF studies were normal. Magnetic resonance imaging of the brain showed changes in keeping with reversible posterior leukoencephalopathy. Consecutive nerve conduction studies were normal, but needle assessment showed marked increased insertional activity and fibrillation potentials in the paraspinal, proximal, and distal muscles. Electrodiagnostic findings were in keeping with multilevel axonal polyradiculopathy. Expedited urine quantitative testing confirmed the diagnosis of AIP. She received heme and supportive therapy with resolution of weakness and seizures but had a spontaneous abortion.

Discussion {#sec1_3}
==========

We present 3 patients with AIP with varying degrees and patterns of motor weakness. In the first patient, motor symptoms were limited to the radial and ulnar nerve innervated muscles. In the second patient, the clinical presentation mimicked Guillain-Barré syndrome (GBS) with progressive weakness leading to respiratory failure and quadriplegia. The electrodiagnostic studies demonstrated absence of both sensory and motor responses with profuse fibrillation potentials and loss of recruitment on needle examination. In the third patient, progressive weakness was associated with marked fibrillation potential activity in the paraspinal, proximal, and distal muscles on EMG in keeping with multilevel axonal polyradiculopathy. All 3 patients had abdominal symptoms and seizures. The second and third cases also had hyponatremia and behavioral changes during the acute phase of the illness. In summary, the presentation of porphyric neuropathy in our patients ranged from focal motor neuropathy to quadriplegia and respiratory failure.

During an acute attack, heme precursors accumulate due to the deficient enzyme, and the excess porphyrin metabolites are then excreted in the urine and feces. In AIP, urinary ALA and porphobilinogen are markedly elevated, leading to the diagnosis as found in these cases \[[@B4]\]. Drugs can provoke an acute porphyric attack, especially those that induce cytochrome P450 proteins (CYP) and those that cause transcription of the rate-limiting enzyme of the heme biosynthetic pathway \[[@B12]\]. The mechanism contributing to the development of nerve dysfunction remains unclear, but recent studies suggest that axonal dysfunction relates to Na+/K+ pump energy dysfunction resulting from the lack of heme availability and a direct neurotoxic effect of porphyrin precursors \[[@B13]\]. Previous reports have demonstrated that hyponatremia has been observed in up to 30% of the patients, due to either primary salt wasting or the syndrome of inappropriate antidiuretic hormone secretion \[[@B3]\].

Motor symptoms are prominent and, as apparent in our first patient, have a predilection for the upper extremities and particularly the radial nerve innervated muscles for unknown reasons \[[@B14]\]. More recent studies have demonstrated that focal weakness, manifesting as isolated wrist drop or foot drop, is an increasingly common finding \[[@B3], [@B11]\]. Reports of nerve conduction studies in patients with porphyric neuropathy have demonstrated decreases in compound action potential amplitudes, particularly in radial and fibular nerves with varying sensory involvement \[[@B6], [@B11], [@B14]\].

The electrophysiologic picture in porphyric neuropathy is consistent with axonal damage similar to changes observed in lead intoxication and other neuropathies \[[@B6], [@B11]\]. Interestingly, a coasting phenomenon is also reported, in which the CMAP amplitude reductions continued to worsen for up to 3--5 months after the initial diagnosis. This phenomenon is also described in some toxic neuropathies, including vitamin B~6~, thalidomide, chemotherapy, and acrylamide \[[@B15]\].

In contrast to motor nerve conduction study findings, sensory nerve conduction findings are scant or show only subtle changes in the patients with AIP \[[@B6], [@B7], [@B15]\]. This predominantly motor pattern in porphyric neuropathy may help in the differentiation from other common metabolic neuropathies, such as those related to diabetes mellitus or kidney impairment, in which sensory involvement is typically more prominent. Cranial nerve involvement has also been described in AIP, most commonly affecting the facial and vagus nerves and leading to facial weakness, dysphagia, and dysarthria \[[@B7]\]. In addition, needle EMG typically shows evidence of widespread active fibrillation potentials and loss of recruitment, particularly in proximal muscles \[[@B5], [@B15]\].

Information on the prognosis of porphyric neuropathy is limited, although the degree of axonal damage probably predicts the ultimate prognosis. Recovery often takes many months with some patients with the GBS variant remaining permanently quadriparetic \[[@B4], [@B5]\]. Treatment for AIP includes both supportive and specific therapies. Once a porphyric attack is diagnosed, precipitating factors or provoking agents should be withdrawn. In addition, glucose supplements or parenteral administration of hematin are suggested \[[@B12], [@B14]\].

Conclusion {#sec1_4}
==========

Porphyric neuropathy is a predominantly motor neuropathy with differing clinical presentations that may mimic various neuropathies, such as GBS, with diffuse axonal involvement or lead neuropathy with specific nerve involvement, such as bilateral radial neuropathy. A diagnosis of porphyria should be considered particularly in those patients with abdominal complaints and seizures.

Statement of Ethics {#sec1_5}
===================

The patients have given their written informed consent to publish their case.

Disclosure Statement {#sec1_6}
====================

The authors have no conflicts of interest to declare.

Funding Sources {#sec1_7}
===============

No funding was received in the preparation of the manuscript.